The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index; 4 of the 26 sources its claims cite were checked for support.
Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance
Open accessAbstract
BACKGROUND: Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus. Interventions that may prevent or delay such occurrences are of great clinical importance. METHODS: We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly, and oral glucose tolerance tests were performed annually. Conversion to diabetes was confirmed on the basis of the results of repeat testing. RESULTS: Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P<0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P<0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per liter], P<0.001), and HbA(1c) (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, P=0.03), a reduced rate of carotid intima-media thickening (31.5%, P=0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P=0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001), and edema was more frequent (12.9% vs. 6.4%, P=0.007). CONCLUSIONS: As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema. (Funded by Takeda Pharmaceuticals and others; ClinicalTrials.gov number, NCT00220961.).
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Claims the paper makes
4 of 26 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Because hyperglycemia plays a central role in the microvascular and macrovascular complications of diabetes, 3,5,6 it is possible that interventions that prevent or delay hyperglycemia may effectively prevent or delay these long-term complications.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Not checked — no full text of the sourcecites [5] source
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
In the opening results passage (page unavailable), the paper says hyperglycemia plays a central role in microvascular complications of type 1 diabetes. A later results passage says differences in glycosylated hemoglobin accounted for much of the cardiovascular benefit of intensive therapy, supporting a role in macrovascular disease. The claim extends these type 1 findings to diabetes generally and states the macrovascular role more definitively than the paper does. (LLM, conf=0.83)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema.”
- Also stated in: § Follow-up · plain
“The hazard ratio for development of diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Follow-up · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007) but not with placebo (124±4.6 to 113±4.0 mg per deciliter [6.9±0.25 to 6.30±0.22mmol per liter], P = 0.90); the difference between groups was not significant.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007) but not with placebo (124±4.6 to 113±4.0 mg per deciliter [6.9±0.25 to 6.30±0.22mmol per liter], P = 0.90); the difference between groups was not significant.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced levels of both alanine aminotranferase and aspartate aminotransferase (P<0.001).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insulin sensitivity as measured with the Matsuda index increased more with pioglitazone than with placebo (4.31±0.24 to 7.65±0.34vs.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced levels of both alanine aminotranferase and aspartate aminotransferase (P<0.001).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007) but not with placebo (124±4.6 to 113±4.0 mg per deciliter [6.9±0.25 to 6.30±0.22mmol per liter], P = 0.90); the difference between groups was not significant.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema.”
- Also stated in: § RESULTS · plain
“Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001)”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Abstract
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HbA 1c (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001)”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 16
- It may state two separate claims as one. 18
- The quote only partly states this claim. 1
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In one study, 9 the use of rosiglitazone decreased the risk of diabetes in adults with impaired glucose tolerance by 62%; given concerns about cardiovascular safety, 14 however, the Food and Drug Administration has restricted the use of rosig litazone therapy to patients in whom glycemic control cannot be achieved with other medications and who cannot take pioglitazone.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Could not verifycites [14] sourceExperimental — accuracy not yet measured
The Results report increased odds of myocardial infarction with rosiglitazone, supporting the cardiovascular-safety concern immediately preceding citation 14. But the supplied claim concerns an FDA restriction: the Discussion describes FDA approval criteria, not a restriction limiting rosiglitazone to patients who cannot use other medications or pioglitazone. Searches for those eligibility conditions found no supporting passage in our copy. (LLM, conf=0.76)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“The natural history of type 2 diabetes mellitus has been well defined, 4 starting with a genetic predisposition and progression from normal glucose tolerance with insulin resistance to impaired glucose tolerance and eventually type 2 diabetes mellitus with the superimposition of beta-cell failure.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Supportedcites [4] source
The “Natural History of Type 2 Diabetes” section describes inherited insulin resistance with initially normal glucose tolerance, progression from normal glucose tolerance to impaired glucose tolerance, and then overt diabetes as β-cell function declines. No page number is supplied in the passages. (LLM, conf=0.94)
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies have shown that the rate of conversion of impaired glucose tolerance to type 2 diabetes mellitus is reduced with lifestyle modification 7 ; the use of metformin, 7 thiazolidinediones, [8][9][10][11] or acarbose 12 ; and bariatric surgery.13”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [7] source
- Not checked — no full text of the sourcecites [8] source
- Not checked — no full text of the sourcecites [9] source
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
This citation is attached to the thiazolidinediones clause, not the other interventions. The Discussion reports that troglitazone reduced diabetes incidence by 75% during treatment, but explicitly says whether other thiazolidinediones are effective remains to be determined. It therefore supports troglitazone, not the class-wide claim without qualification. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [11] source
- Not checked — no full text of the sourcecites [12] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Follow-up
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During a median follow-up period of 2.4 years (mean, 2.2), diabetes developed in 50 of the 299 patients in the placebo group (16.7%) and in 15 of the 303 patients in the pioglitazone group (5.0%).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Follow-up
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Protection from diabetes with pioglitazone was of similar magnitude (with no significant heterogeneity) in subgroups defined by sex, age, weight, race or ethnic group, and fasting glucose level, as well as in patients with both impaired glucose tolerance and impaired fasting glucose and those with isolated impaired glucose tolerance (Fig. 3).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither pioglitazone nor placebo altered levels of low-density lipoprotein cholesterol.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nine fractures occurred in 8 of the patients receiving pioglitazone (3%) and eight fractures occurred in 7 of the patients receiving placebo (2.6%) (Table 4 in the Supplementary Appendix).All fractures were associated with trauma.”
- Also stated in: § Discussion · plain
“Although an increased incidence of fractures has been reported with the use of thiazolidinediones, in this study, the incidence was similar in both groups, and all fractures were related to trauma.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
Strength:plain· not yet calibratedn = 8Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Events related to the cardiovascular system numbered 23 in the placebo group (7.7%) and 26 in the pioglitazone group (8.6%) (Table 3 in the Supplementary Appendix), with 1 case of congestive heart failure in each group (0.3%).”
- Also stated in: § Discussion · plain
“Physician-reported congestive heart failure developed in only one patient in each group.”
- Also stated in: § Discussion · plain
“For the comparison of placebo and pioglitazone regarding frequency of edema, cardiovascular events, and total events, P = 0.007, P = 0.80, and P = 0.03, respectively.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ratio of urinary microalbumin to creatinine was low at baseline; during the study it fell slightly and similarly in the two groups (1.85±0.2 to 1.53±0.2mg per gram in the pioglitazone group vs. 1.47±0.3 to 1.25±0.3mg per gram in the placebo group, P = 0.20).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although pioglitazone is a well-documented insulin sensitizer, insulin resistance was reduced according to the Matsuda index of insulin sensitivity measured during the oral glucose-tolerance test but not according to measurement of insulin sensitivity during the frequent-sampling intravenous glucose-tolerance test.”
- Also stated in: § Discussion · plain
“Insulin sensitivity as determined with the use of an intravenous glucose-tolerance test with frequent sampling in a subgroup of 191 patients was not altered in either group.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pioglitazone was associated with lower diastolic blood pressure, higher levels of HDL cholesterol, and reduced rates of carotid intima-media thickening, as compared with placebo.”
- Also stated in: § Discussion · plain
“Use of pioglitazone improved diastolic blood pressure, HDL cholesterol levels, and serum levels of alanine aminotranferase and aspartate aminotransferase, and it slowed progression of carotid intima-media thickening.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One unexplained sudden death oc-curred in the placebo group, and three deaths occurred in the pioglitazone group (one unexplained sudden death, one death from biliary carcinoma, and one death from a carcinoid tumor).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Edema and weight gain were greater with pioglitazone than with placebo, as reported previously, 8,40 and edema largely accounted for the increase in adverse events associated with pioglitazone.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We calculated that enrollment of approximately 600 patients was required to achieve 90% power, if treatment with pioglitazone decreased the rate of conversion from impaired glucose tolerance to type 2 diabetes mellitus by 50%.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In one study, 9 the use of rosiglitazone decreased the risk of diabetes in adults with impaired glucose tolerance by 62%; given concerns about cardiovascular safety, 14 however, the Food and Drug Administration has restricted the use of rosig litazone therapy to patients in whom glycemic control cannot be achieved with other medications and who cannot take pioglitazone.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [9] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, further glycemic separation between groups over time would presumably have a beneficial effect on microvascular disease.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Since neither approach produced statistically significant evidence of bias due to missing data, the primary and secondary analyses were performed without data imputation.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Statistical Analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Takeda Pharmaceuticals provided financial support for the study but had no access to the data.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Study Design
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All results were transmitted to the Data Coordinating Center in Phoenix, Arizona, where they were recorded and audited and then sent to the Data Analysis Center in San Antonio.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Study Design
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was conducted in accordance with the protocol.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Study Design
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Troglitazone was reported to be associated with a 55% decrease in the rate of conversion to diabetes among women with prior gestational diabetes, 11 but this agent is no longer available.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [11] source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The small difference in levels of HbA 1c between the two groups is not surprising, given the low baseline level of HbA 1c in patients with impaired glucose tolerance.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of adherence to the study regimen, assessed by means of pill counts, was greater than 80% in both groups.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Follow-up
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, if development of diabetic hyperglycemia can be delayed or prevented, it is plausible that the onset of microvascular complications might be slowed.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is not feasible to conduct studies of microvascular outcomes in patients with impaired glucose tolerance because of the large sample and long study duration required.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Loss to follow-up was relatively high in both study groups (24% in the placebo group and 30% in the pioglitazone group, not a significant dif-ference).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Microvascular and macrovascular complications are common in type 2 diabetes mellitus and are related to both the severity and the duration of hyperglycemia. 3”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [3] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > METHODS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, the greater the weight gain, the greater the improvements in betacell function and insulin sensitivity, and thus the greater the reduction in HbA 1c .26,35,36”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Carotid intima-media thickening is highly correlated with cardiovascular events, and changes in this measure over time have predictive value beyond that of standard markers of risk.18,38”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Impaired glucose tolerance is associated with increased rates of cardiovascular disease.
“Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“There is strong evidence that oral glucose-lowering medications approved for DM reduce the progression of prediabetes to DM.888–896”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [890]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Metformin can also be combined with linagliptin to decrease DM incidence over that observed with metformin alone.890”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [890]
Experimental — accuracy not yet measuredIn the citing paper
“However, these hypotheses are based on results from the Swedish Obese Subjects Study in which subjects were not randomized and the control group was contemporaneously matched, only received conventional treatment, and differed by a number of characteristics at baseline.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [174]
In the citing paper
“Other studies have reported lower conversion rates29 (19% in controls in the DPP Outcomes study).15”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [29]
In the citing paper
“Pioglitazone showed effectiveness in the ACT NOW Study on obese people with IGT. The risk of diabetes decreased by >70% and the drug was associated with improved diastolic blood pressure, improved HDL-cholesterol and a reduced rate of carotid intima-media thickening. However, weight gain was greater with pioglitazone (~3 kg compared to placebo) and edema was more frequently reported (13% vs. 6%).”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [29]
In the citing paper
“In Actos Now for Prevention of Diabetes (ACT NOW), treatment with pioglitazone 45 mg per day reduced incident diabetes 72% over 2.4 years in patients with IGT and at least one other risk factor for T2DM and BMI ≥ 25 kg/m2.203”
From The Vasculature in Prediabetes (2018) · cites this paper as [203]
In the citing paper
“Thiazolidinediones prevent the development of diabetes in individuals with IFG or IGT.”
From The Vasculature in Prediabetes (2018) · cites this paper as [203]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Placebo fracture percentage does not match its patient count
MinorSeven of 299 placebo patients is about 2.34%, which rounds to 2.3% at the reported precision, not 2.6%.
Reported 2.6 · recomputed 2.341137
“eight fractures occurred in 7 of the patients receiving placebo (2.6%)”
Pioglitazone baseline BMI differs between sections
MinorTable 1 gives the pioglitazone group's baseline mean BMI as 33.0, whereas the later baseline-to-follow-up values give it as 34.1.
“Mean BMI 33.0±0.434.5±0.40.44”
“34.1±0.4 to 35.5±0.4,and 40.0±0.8 to 41.9±0.7%,respectively), but the increments were greater with pioglitazone”
Triglyceride conversion is too high
MinorUsing the paper's triglyceride conversion factor of 0.01129, 129 mg per deciliter is about 1.46 mmol per liter, not 7.2.
Reported 7.2 · recomputed 1.45641
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007)”
HDL cholesterol conversion is too high
MinorThe paper specifies a cholesterol conversion factor of 0.02586, which converts 40 mg per deciliter to about 1.03 mmol per liter, not 2.2.
Reported 2.2 · recomputed 1.0344
“The change in high-density lipoprotein (HDL) cholesterol was greater with pioglitazone (40±1 to 48±1 mg per deciliter [2.2±0.06 to 2.7±0.06 mmol per liter])”
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Japanese Clinical Practice Guideline for Diabetes 2016
Haneda, M., Noda, M., Origasa, H., Noto, H., Yabe, D., Fujita, Y., Goto, A., Kondo, T., & Araki, E. (2018) · Journal of Diabetes Investigation · doi:10.1111/jdi.12810 · Cited by 184
Brannick, B., Wynn, A., & Dagogo-Jack, S. E. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216654227 · Cited by 189
Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk
Goldfine, A. B., & Shoelson, S. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88884 · Cited by 176
“However, many immunomodulation therapies are used safely in autoimmune and rheupeutically for glucose lowering in T2D and for diabetes prevention (63, 64) and partition triglycerides out of the liver in patients with steatosis (65).”
New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis
Méndez‐Sánchez, N., Cruz-Ramón, V., Ramírez-Pérez, O., Hwang, J. P., Barranco-Fragoso, B., & Córdova‐Gallardo, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072034 · Cited by 177
“This drug can reduce subclinical inflammation, improve AT and hepatic insulin signaling, and enhance insulin action [131,132].”
BackgroundMerlotti, C., Morabito, A., & Pontiroli, A. E. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12270 · Cited by 169
3. Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes—2020
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc20-s003 · Cited by 162
5. Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes—2018
American Diabetes Association (2017) · Diabetes Care · doi:10.2337/dc18-s005 · Cited by 164
Interleukin-1 Receptor Antagonist: A New Therapy for Type 2 Diabetes Mellitus
Akash, M. S. H., Shen, Q., Rehman, K., & Chen, S. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23057 · Cited by 158
Interventions for Reversing Prediabetes: A Systematic Review and Meta-Analysis
Galaviz, K. I., Weber, M. B., Suvada, K., Gujral, U. P., Wei, J., Merchant, R., Dharanendra, S., Haw, J. S., Narayan, K. M. V., & Ali, M. K. (2022) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2021.10.020 · Cited by 149
Dupuis, L., Dengler, R., Heneka, M. T., Meyer, T., Zierz, S., Kassubek, J., Fischer, W., Steiner, F., Lindauer, E., Otto, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037885 · Cited by 159
“Pioglitazone displays pleiotropic effects on energy metabolism through insulin sensitization, decreased glycaemia, and decreased circulating levels of liver enzymes and has been shown to be safe even in non-diabetic patients [7,8,9,10].”
BackgroundCinnamon extract lowers glucose, insulin and cholesterol in people with elevated serum glucose
Anderson, R. A., Zhan, Z., Luo, R., Guo, X., Guo, Q., Zhou, J. J., Kong, J., Davis, P. A., & Stoecker, B. J. (2015) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2015.03.005 · Cited by 155
Pioglitazone for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis
Lee, M., Saver, J. L., Liao, H.-W., Lin, C.-H., & Ovbiagele, B. (2017) · Stroke · doi:10.1161/strokeaha.116.013977 · Cited by 147
“placebo, reduces the risk of conversion of impaired glucose tolerance to diabetes mellitus.(26) Pioglitazone, as compared”
BackgroundType 2 Diabetes Can Be Prevented With Early Pharmacological Intervention
DeFronzo, R. A., & Abdul‐Ghani, M. A. (2011) · Diabetes Care · doi:10.2337/dc11-s221 · Cited by 150
“Although the pioglitazone dose in ACT NOWwas 45 mg/day, lower doses (15–30mg/day) improve insulin sensitivity and insulin secretion (160a) in type 2 diabetes and were effective in decreasing IGT conversion to type 2 diabetes and in reverting IGT to NGT in ACT NOW (21).”
BackgroundInfluentialSelf-citationCardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived?
Abdul-Ghani, M. A., DeFronzo, R. A., Prato, S. D., CHILTON, R. J., Singh, R., & Ryder, R. E. J. (2017) · Diabetes Care · doi:10.2337/dc16-2736 · Cited by 146
“and markedly enhances and preserves b-cell function (50,51,59).”
BackgroundSelf-citationKelly, A. S., Metzig, A. M., Rudser, K. D., Fitch, A., Fox, C. K., Nathan, B. M., Deering, M. M., Schwartz, B. L., Abuzzahab, M. J., Gandrud, L. M., et al. (2011) · Obesity · doi:10.1038/oby.2011.337 · Cited by 143
“Area-under-the-curve (AUC) for glucose and insulin, the whole body insulin sensitivity index (WBISI/Matsuda index), and β-cell function were calculated from the OGTT as previously described (22).”
MethodPersonalized Management of Hyperglycemia in Type 2 Diabetes
Raz, I., Riddle, M. C., Rosenstock, J., Buse, J. B., Inzucchi, S. E., Home, P., Prato, S. D., Ferrannini, E., Chan, J. C. N., Leiter, L. A., et al. (2013) · Diabetes Care · doi:10.2337/dc13-0512 · Cited by 150
Self-citation3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2024
ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Gaglia, J. L., Hilliard, M. E., Johnson, E. L., Khunti, K., et al. (2023) · Diabetes Care · doi:10.2337/dc24-s003 · Cited by 157
3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2025
ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Early, K. B., Bruemmer, D., Ebekozien, O. A., Echouffo-Tcheugui, J. B., Ekhlaspour, L., et al. (2024) · Diabetes Care · doi:10.2337/dc25-s003 · Cited by 171
Cefalu, W. T., Buse, J. B., Tuomilehto, J. O., Fleming, G. A., Ferrannini, E., Gerstein, H. C., Bennett, P. H., Ramachandran, A., Raz, I., Rosenstock, J., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0873 · Cited by 148
“In ACT NOW, overweight adults with IGT were randomly assigned to either pioglitazone titrated to 45 mg daily or placebo.”
BackgroundInfluentialFiorentino, T. V., Marini, M. A., Andreozzi, F., Arturi, F., Succurro, E., Perticone, M., Sciacqua, A., Hribal, M. L., Perticone, F., & Sesti, G. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2573 · Cited by 138
“Variable NGT With 1-h Glucose <155 mg/dL (1) NGT With 1-h Glucose >155 mg/dL (2) Isolated IFG (3) IGT (4) P”
BackgroundThe Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus
Yau, H., Rivera, K., Lomonaco, R., & Cusi, K. J. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0378-8 · Cited by 143
Stevens, J., Khunti, K., Harvey, R. C., Johnson, M., Preston, L., Woods, H. B., Davies, M. J., & Goyder, E. (2015) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2015.01.027 · Cited by 142
Retnakaran, R. R., Kramer, C. K., Choi, H., Swaminathan, B., & Zinman, B. (2014) · Diabetes Care · doi:10.2337/dc14-0893 · Cited by 140
Cusi, K. J. (2016) · Diabetologia · doi:10.1007/s00125-016-3952-1 · Cited by 141
“Pioglitazone also prevents the progression from impaired glucose tolerance to diabetes [46], and one may speculate that this effect is tied to its ability to reverse NAFLD/NASH [47].”
BackgroundThe Vasculature in Prediabetes
Wasserman, D. H., Wang, T. J., & Brown, N. J. (2018) · Circulation Research · doi:10.1161/circresaha.118.311912 · Cited by 137
“4 years in patients with IGT and at least one other risk factor for T2DM and BMI ≥25 kg/m(2).(203) Pioglitazone also reduced PAI-1 and slowed the rate of progression of carotid intima– media thickening.”
BackgroundSelph, S., Dana, T., Blazina, I., Bougatsos, C., Patel, H., & Chou, R. (2015) · Annals of Internal Medicine · doi:10.7326/m14-2221 · Cited by 134
“Meta-analysis of the effect of lifestyle interventions on incidence of progression to DM. Knowler et al, 2002 (7)* Katula et al, 2013 (88) Kosaka et al, 2005 (8)* Li et al, 2014 (38) Lindahl et al, 2009 (87) Penn et al, 2009 (84) Ramachandran et al, 2006 (10)* Saito et al, 2011 (40) Sakane et al, 2011 (86) Tuomilehto…”
BackgroundInfluentialAmerican Diabetes Association Professional Practice Committee (2021) · Diabetes Care · doi:10.2337/dc22-s003 · Cited by 167
de Jong, M., van der Worp, H. B., van der Graaf, Y., Visseren, F. L. J., & Westerink, J. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0617-4 · Cited by 137
“For example, pioglitazone has been associated with a reduction of coronary inflammation [43], alterations in the coronary atherosclerotic core composition and in particular a reduction of the necrotic core [44, 45], a reduction of neointima volume after stent implantation [46], and a decrease of carotid intima-media t…”
BackgroundPerreault, L., Temprosa, M., Mather, K. J., Horton, E., Kitabchi, A., Larkin, M., Montez, M. G., Thayer, D., Orchard, T. J., Hamman, R. F., et al. (2014) · Diabetes Care · doi:10.2337/dc14-0656 · Cited by 131
“For example, two separate investigations (18,19) have reported slowing in the progression of carotid intima-media thickening by 30– 70% in people with prediabetes or a history of gestational diabetes treated with pioglitazone for ,3 years.”
BackgroundSelf-citationMeta-analysis investigating the role of interleukin-6 mediated inflammation in type 2 diabetes
Bowker, N., Shah, R. L., Sharp, S. J., Luan, J., Stewart, I. D., Wheeler, E., Ferreira, M. A. R., Baras, A., Wareham, N. J., Langenberg, C., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103062 · Cited by 134
“In comparison, relatively safe and inexpensive lifestyle interventions [64], metformin [64] or other hypoglycaemic drugs [65] have been associated with reductions in the incidence of diabetes ranging from 30% to 70% in previous primary prevention trials.”
BackgroundIn Vivo Actions of Peroxisome Proliferator–Activated Receptors
Eldor, R., DeFronzo, R. A., & Abdul‐Ghani, M. A. (2013) · Diabetes Care · doi:10.2337/dcs13-2003 · Cited by 128
“Thiazolidinediones prevent T2DM in high-risk individuals Six large prospective, randomized, doubleblind, placebo-controlled studies (TRIPOD [126], PIPOD [123], DPP [125], DREAM [124], CANOE [128], and ACT NOW [127]) have provided conclusive evidence that thiazolidinediones dramatically reduce by 52–72% conversion of p…”
BackgroundInfluentialSelf-citation
Metadata
- Authors
- DeFronzo, R. A., Tripathy, D., Schwenke, D. C., Banerji, M., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Hodis, H. N., Kitabchi, A. E., Mack, W. J., Mudaliar, S., Ratner, R. E., Williams, K., Stentz, F. B., Musi, N., & Reaven, P. D.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Texas Diabetes Institute (US)
- Phoenix VA Health Care System (US)
- Pennington Biomedical Research Center (US)
- University of Southern California (US)
- Georgetown University (US)
- University of California San Diego (US)
- University of Tennessee Health Science Center (US)
- MedStar Health Research Institute (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-03-24
- Volume
- 364
- Issue
- 12
- Pages
- 1104-1115
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2131330057
- Semantic Scholar
- 2537f2b5521882869eda52ee137db9e85431749f
- Cited by
- 766
- References
- 42
- Citations by year
- 2026: 26 · 2025: 20 · 2024: 44 · 2023: 35 · 2022: 35 · 2021: 49 · 2020: 45 · 2019: 45 · 2018: 58 · 2017: 54 · 2016: 53 · 2015: 61 · 2014: 61 · 2013: 69 · 2012: 69
- FWCI
- 49.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01-RR00221, M01RR000043)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- pioglitazone, impaired glucose tolerance, type 2 diabetes prevention, thiazolidinediones, glucose tolerance, fasting blood glucose, HbA1c, carotid intima-media thickening, diastolic blood pressure, HDL cholesterol, cardiovascular risk, PPARγ agonists, statins, fibrates, nicotinic acid, fenofibrate
- MeSH terms
- Pioglitazone, Adolescent, Adult, Blood Glucose, Blood Pressure, Diabetes Mellitus, Type 2, Double-Blind Method, Edema, Follow-Up Studies, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin Resistance, Middle Aged, Weight Gain, Life Tables, Proportional Hazards Models, Glucose Intolerance, Thiazolidinediones, Kaplan-Meier Estimate, Young Adult
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