Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
Open accessAbstract
BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. RESULTS: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). CONCLUSIONS: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)
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The ACCORD trial found a modest but significant reduction in DPN risk with intensive glucose intervention after 5 years in T2D.
“The ACCORD trial in individuals with T2D reported a modest but significant DPN risk reduction with intensive glycemia intervention after 5 years of follow-up,69”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [69]
The paper identifies its trial as ADVANCE (title page, p. 2), not ACCORD. Its secondary-outcomes table (p. 10) reports new or worsening neuropathy in 42.2% of the intensive-control group versus 41.5% of the standard-control group, with a confidence interval spanning no effect. It therefore does not report the claimed significant reduction in DPN risk. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe DiRECT Study reported that a very low-calorie formula diet (825-853 kcal/d) followed by stepped food reintroduction achieved remission of type 2 diabetes (HbA1C <6.5% without diabetes medications for at least 2 months) among 46% of participants in the intervention group vs 4% in the control group at 12 months (odds ratio, 19.7 [95% CI, 7.8-49.8]).
“The DiRECT Study, an open-label, cluster-randomized trial of 306 individuals from 49 primary care practices in the UK, reported that a very low–calorie formula diet (825–853 kcal/d) followed by stepped food reintroduction achieved remission of type 2 diabetes (HbA1C <6.5% without diabetes medications for at least 2 months) among 46% of participants in the intervention group vs 4% in the control”
From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [34]
Split into 2 atoms — 0 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredSome newer therapies have a lower hypoglycemia risk, which may allow more people to safely reach individualized A1C targets.
“As discussed in Q12. How can glycemic targets be achieved in persons with T2D? as well as in the AACE Comprehensive Type 2 Diabetes Management Algorithm,73 some newer therapies carry a lower risk of hypoglycemia, which may enable more persons to safely achieve individualized target A1C levels.69,88–90”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [69]
The Discussion (p. 13) reports that severe hypoglycemia was relatively uncommon despite the trial’s lower achieved A1C, and less frequent than in an earlier trial. The Results (p. 2) show that the intensive strategy reached an average A1C of 6.5%, but this paper does not establish that newer therapies have a lower hypoglycemia risk or that they enable more people to reach individualized targets safely. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe risks of intensive glycemic control may be avoided by using agents not associated with hypoglycemia, especially in people with frequent severe hypoglycemia, hypoglycemia unawareness, long diabetes duration, advanced atherosclerosis, advanced age, or terminal illness.
“The potential risks of intensive glycemic control may be obviated by incorporating agents that are not associated with hypoglycemia, especially in persons with frequent severe hypoglycemia, hypoglycemia unawareness, or a very long duration of DM, and particularly in the presence of established and advanced atherosclerosis, advanced age, and terminal illness.69,70,76–81”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [69]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredA relationship between mortality and randomization to intensive glucose control was not observed in ADVANCE or VADT.
“A relationship between mortality and randomization to intensive glucose control was not observed in ADVANCE or VADT, although VADT was underpowered to explore this relationship.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
The ADVANCE Results (p. 2) report no significant difference in death from any cause between intensive and standard glucose control. Our copy does not report mortality findings from VADT or say whether VADT was underpowered to assess that relationship (searched: VADT, Veterans Affairs Diabetes Trial, mortality). (LLM, conf=0.90)
Experimental — accuracy not yet measured
In each of ACCORD, ADVANCE, and VADT, subjects randomly assigned to the intensive arm experienced more episodes of hypoglycemia than did those randomly assigned to the standard treatment arm.
“In each, subjects who were randomly assigned to the intensive arm experienced more episodes of hypoglycemia than did those who were randomly assigned to the standard treatment arm.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
The Effects on Hypoglycemia section (p. 10) reports more severe and minor hypoglycemia in ADVANCE’s intensive-control group than in its standard-control group. This paper does not establish the corresponding comparison for ACCORD or VADT, so it supports only the ADVANCE part of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn most people with type 1 or type 2 diabetes, an A1C ≤7.0% should be targeted to reduce the risk of microvascular complications and, if implemented early in the course of disease, CV complications.
“In most people with type 1 or type 2 diabetes, an A1C ≤7.0% should be targeted to reduce the risk of microvascular [Grade A, Level 1A (1,2,22,23)] and, if implemented early in the course of disease, CV complications [Grade B, Level 3 (23)].”
From Targets for Glycemic Control (2018) · cites this paper as [23]
The Results (p. 2) show that intensive glucose control reduced major microvascular events in patients with type 2 diabetes, primarily through fewer cases of nephropathy. The study did not include people with type 1 diabetes, and the Discussion (pp. 11–12) reports no significant reduction in major cardiovascular events. It does not establish a cardiovascular benefit from starting the target early in the disease course. (LLM, conf=0.89)
Experimental — accuracy not yet measuredIn the ADVANCE trial, intensive glucose control aimed at reducing A1C ≤6.5% significantly reduced the incidence of major microvascular events, mainly through a 21% relative reduction in nephropathy, but had no beneficial effect on major CV events or all-cause mortality during the trial or subsequent median 5.4-year follow-up.
“There was significant reduction in the incidence of major microvascular events in the intensive control group, mainly through a 21% relative reduction in nephropathy (23); however, no beneficial effect of intensive glucose lowering was found on major CV events or allcause mortality either during the trial or the subsequent median observational follow up of 5.4 years (24).”
From Targets for Glycemic Control (2018) · cites this paper as [23]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIntensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes and type 2 diabetes.
“Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large, randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes (52,53) and type 2 diabetes (1,(54)(55)(56)(57)(58)(59).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [55]
In the Results (p. 9), intensive glucose control in patients with type 2 diabetes reduced new-onset microalbuminuria and development of macroalbuminuria, supporting the albuminuria portion of the claim. The paper does not report a reduction in eGFR; the same passage reports no effect on doubling of serum creatinine. This trial studied type 2 diabetes, while the sentence cites other studies for type 1 diabetes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLowering blood glucose itself helps prevent CKD and its progression.
“Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of type 1 diabetes, while a variety of agents were used in clinical trials of type 2 diabetes, supporting the conclusion that lowering blood glucose itself helps prevent CKD and its progression.”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [55]
The Discussion (p. 11) reports a 21% reduction in new or worsening nephropathy with intensive glucose control in people with type 2 diabetes, supporting a benefit for diabetic kidney complications. The renal results (p. 9) show that this was driven chiefly by less macroalbuminuria; they found no effect on doubling of serum creatinine and did not establish that lowering glucose itself, independent of the drugs used, prevents CKD progression generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe ADVANCE and VADT trials found modest reduction in nephropathy with intensive glycemic management; ACCORD was stopped after a median of 3.5 years due to higher mortality in the intervention arm.
“The ADVANCE and VADT trials found modest reduction in nephropathy with intensive glycemic management; ACCORD was stopped after a median of 3.5 years due to higher mortality in the intervention arm (51-55).”
From 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. (2026) · cites this paper as [52]
The Discussion (p. 11) reports a 21% relative reduction in new or worsening nephropathy in ADVANCE. The Discussion (p. 12) also reports that excess mortality led to premature termination of ACCORD’s intensive glucose-control strategy. Our copy does not establish a nephropathy reduction in VADT or the claimed median of 3.5 years for ACCORD. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAn HbA1c target of ≤6.5% probably decreased the incidence of moderately increased albuminuria and kidney failure.
“Six studies compared a target HbA1c of # 6.5% to higher HbA1c targets (standard glycemic control) and found that an HbA1c target of # 6.5% probably decreased the incidence of moderately increased albuminuria, and kidney failure (Supplementary Table S12 239,240,242 -244,252 )”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [244]
The Results (p. 9) report significantly fewer cases of new-onset microalbuminuria with intensive control targeting HbA1c ≤6.5%. They report only a nonsignificant trend toward less renal-replacement therapy or death from renal causes (p. 9), so this trial does not establish a decrease in kidney failure. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPoor control, defined as a hemoglobin A1c level >9.0%, contributes to complications, including nephropathy, retinopathy, and neuropathy.
“Poor control, defined as a hemoglobin A1c (HbA1c) level >9.0%, contributes to complications, including nephropathy [1-6], retinopathy [4,7], and neuropathy [4,8].”
From An Assessment of How Clinicians and Staff Members Use a Diabetes Artificial Intelligence Prediction Tool: Mixed Methods Study (2023) · cites this paper as [1]
The Results (p. 2) show that intensive glucose control reduced nephropathy, supporting a link between glycemic control and that complication. The paper does not define poor control as HbA1c >9.0%; it reports no significant effect on retinopathy (Results, p. 2), and its secondary-outcomes table (p. 10) does not show a reduction in neuropathy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredLowering glucose concentrations can reduce rates of microvascular complications and possibly macroangiopathic complications.
“Similarly, it has been accepted that strategies aimed at lowering glucose concentrations can lead to lower rates of microvascular and perhaps macroangiopathic complications.69”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [69]
Between ACCORD, ADVANCE, and VADT, a total of 24,000 patients with high cardiovascular risk were randomly assigned to either intensive glycemic control or standard therapy.
“Between them, a total of 24,000 patients with high cardiovascular risk were randomly assigned to either intensive glycemic control or standard therapy (3–5).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
In people with type 2 diabetes, an A1C ≤6.5% may be targeted to reduce the risk of CKD and retinopathy, if they are assessed to be at low risk of hypoglycemia based on class of antihyperglycemic medication(s) utilized and the person's characteristics.
“In people with type 2 diabetes, an A1C ≤6.5% may be targeted to reduce the risk of CKD [Grade A, Level 1A (23)] and retinopathy [Grade A, Level 1A (21)], if they are assessed to be at low risk of hypoglycemia based on class of antihyperglycemic medication(s) utilized and the person's characteristics [Grade D, Consensus].”
From Targets for Glycemic Control (2018) · cites this paper as [23]
The DCCT in individuals with type 1 diabetes and the UKPDS, ACCORD, ADVANCE, and VADT studies in type 2 diabetes all sought to address whether intensive glycemic management reduced cardiovascular disease events.
“The DCCT in individuals with type 1 diabetes and the UKPDS, ACCORD, ADVANCE, and VADT studies in type 2 diabetes all sought to address whether intensive glycemic management reduced cardiovascular disease (CVD) events (43,51,52,54).”
From 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. (2026) · cites this paper as [52]
Validated instruments like the Michigan Neuropathy Screening Instrument, modified Toronto Clinical Neuropathy Scale, Utah Early Neuropathy Scale, and Neuropathy Disability Score are feasible and can be standardized in large DM cohorts.
“The use of validated clinical instruments such as the Michigan Neuropathy Screening Instrument (most widely used in large cohorts of persons with T1D and T2D),69,417,546,550,569–571 the modified Toronto Clinical Neuropathy Scale,572 the Utah Early Neuropathy Scale,573 or the Neuropathy Disability Score574 are feasible and can be done in a standardized fashion in large cohorts of persons with DM.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [69]
The Methods (p. 2) describe a large cohort with type 2 diabetes, and the secondary-outcomes table (p. 10) reports new or worsening neuropathy. Neither passage identifies a neuropathy screening instrument or addresses whether the named instruments are feasible and standardized in large cohorts. Searches for their names, MNSI, and neuropathy assessment found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredVADT was underpowered to explore the relationship between mortality and randomization to intensive glucose control.
“A relationship between mortality and randomization to intensive glucose control was not observed in ADVANCE or VADT, although VADT was underpowered to explore this relationship.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
The Results (p. 2) report no significant mortality effect in ADVANCE, and the Statistical Analysis (p. 4) discusses power for ADVANCE’s primary outcomes. Neither passage addresses whether VADT was underpowered to examine mortality; searches for VADT and Veterans Affairs trial power found no such statement in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measuredAll three trials clearly demonstrated that an episode of severe hypoglycemia was associated with an increased risk of subsequent mortality.
“All three trials clearly demonstrated that an episode of severe hypoglycemia was associated with an increased risk of subsequent mortality.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
The Effects on Hypoglycemia (p. 10) report more severe episodes with intensive control and one fatal episode, but do not assess mortality after an episode. The mortality results (pp. 2, 8) compare treatment groups, not people with and without severe hypoglycemia. Our copy reports the ADVANCE trial and does not establish the claimed association across three trials. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe role of intensive glycemic control for reducing cardiovascular risk has not been established as clearly in people with type 2 diabetes mellitus.
“its role for reducing cardiovascular risk has not been established as clearly in people with T2DM [11–13].”
From Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017 (2018) · cites this paper as [11]
Recent trials in type 2 diabetes that targeted HbA1c below 6.5% with multiple drugs showed inconsistent benefits and no macrovascular advantage over strategies leaving HbA1c 0.8-1.1% higher.
“recent studies that used multiple medications to treat type 2 diabetes and aimed for HbA 1c concentrations ,6.5% (48 mmol/mol) have not demonstrated consistent benefits and failed to observe any benefit with regard to macrovascular disease, compared with interventions that achieved HbA 1c values 0.8% to 1.1% higher (50)(51)(52).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [51]
In the ADVANCE trial, while the gliclazide-based more intensive control strategy did not significantly improve cardiovascular outcomes, there were no major cardiovascular safety concerns observed.
“While the gliclazidebased more intensive control strategy did not significantly improve CV outcomes, there were no major CV safety concerns observed.”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [128]
In ADVANCE, intensive control significantly reduced the total number of major macrovascular events and major microvascular events, but only the reduction in microvascular events was statistically significant.
“Intensive control significantly reduced the total number of major macrovascular events (death from cardiovascular causes, non-fatal myocardial infarction, nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), but only the reduction in microvascular events was statistically significant.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [435]
The ACCORD trial was stopped prematurely at 3.5 years due to significantly increased total mortality in the intensive treatment group: 257 vs 203 (P=0.04) for deaths from any cause and 135 vs 94 (P=0.02) for cardiovascular deaths.
“The trial was stopped prematurely at 3.5 years due to a significantly increased total mortality in the intensive treatment group: 257 vs. 203 (P ¼ 0.04) for deaths due to any cause and 135 vs. 94 (P ¼ 0.02) for deaths due to cardiovascular causes.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [435]
In ACCORD, there were significantly more cases of hypoglycaemia requiring assistance and significantly more weight gain in the intensive group.
“There were significantly more cases of hypoglycaemia requiring assistance in the intensive group, who also experienced significantly more weight gain.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [435]
Weight gain and hypoglycaemia were less frequent in ADVANCE than in ACCORD.
“Weight gain and hypoglycaemia were less frequent than in the ACCORD study.”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [435]
Studies testing lifestyle and drug interventions to delay diabetes onset have generally shown benefit, with lifestyle outperforming all medications except thiazolidinediones.
“These trials have more or less uniformly demonstrated a benefit, with lifestyle more efficacious than all medications with the exception of the thiazolidinediones140–152.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [147]
Current studies have failed to demonstrate a beneficial effect of intensive diabetes therapy on cardiovascular disease in type 2 diabetes.
“current studies have failed to demonstrate a beneficial effect of intensive diabetes therapy on CVD in type 2 diabetes (11–13)”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [12]
None of the studies has demonstrated a benefit of intensive glycemic control on their primary cardiovascular disease outcomes.
“However, none of the studies has demonstrated a benefit of intensive glycemic control on their primary CVD outcomes.”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [12]
The ADVANCE trial and the Veterans Affairs Diabetes Trial did not demonstrate any excess total or cardiovascular disease mortality with intensive regimens that achieved A1C levels comparable with the 6.5% in ACCORD.
“Results from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial and the Veterans Affairs Diabetes Trial, both of which had different interventions and study populations than ACCORD, did not demonstrate any excess total or CVD mortality with intensive regimens that achieved A1C levels comparable with the 6.5% in ACCORD (12,13).”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [12]
Concerns raised by the University Group Diabetes Program that sulfonylureas, as a drug class, may increase cardiovascular disease mortality in type 2 diabetes were not substantiated by the UKPDS or ADVANCE study.
“Concerns raised by the UGDP that sulfonylureas, as a drug class, may increase CVD mortality in type 2 diabetes were not substantiated by the UKPDS or ADVANCE study (6,12).”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [12]
In ACCORD, ADVANCE, and VADT, subjects randomly assigned to the intensive arm experienced more episodes of hypoglycemia than did those randomly assigned to the standard treatment arm.
“In each, subjects who were randomly assigned to the intensive arm experienced more episodes of hypoglycemia than did those who were randomly assigned to the standard treatment arm.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
There is growing evidence that patients with type 2 diabetes might be particularly vulnerable to adverse events associated with hypoglycemia.
“There is growing evidence that patients with type 2 diabetes might be particularly vulnerable to adverse events associated with hypoglycemia.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
A relationship between mortality and randomization to intensive glucose control was not observed in ADVANCE or VADT, although VADT was underpowered to explore this relationship.
“A relationship between mortality and randomization to intensive glucose control was not observed in ADVANCE or VADT, although VADT was underpowered to explore this relationship.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
All three trials clearly demonstrated that an episode of severe hypoglycemia was associated with an increased risk of subsequent mortality.
“All three trials clearly demonstrated that an episode of severe hypoglycemia was associated with an increased risk of subsequent mortality.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [5]
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Lv, J., & Zhang, L. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8871-2_1 · Cited by 1,119 · see citing works
Ahmad, E., Lim, S., Lamptey, R., Webb, D. R., & Davies, M. J. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01655-5 · Cited by 1,120 · see citing works
Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum?
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Rosenstock, J., Perkovic, V., Johansen, O. E., Cooper, M. E., Kahn, S. E., Marx, N., Alexander, J. H., Pencina, M., Toto, R. D., Wanner, C., et al. (2019) · JAMA · doi:10.1001/jama.2018.18269 · Cited by 1,084 · see citing works
DEPARTMENT OF HEALTH & HUMAN SERVICES
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Sjöström, L., Peltonen, M., Jacobson, P., Ahlin, S., Andersson-Assarsson, J., Anveden, Å., Bouchard, C., Carlsson, B., Karason, K., Lönroth, H., et al. (2014) · JAMA · doi:10.1001/jama.2014.5988 · Cited by 1,054 · see citing works
Standards of Medical Care in Diabetes—2012
(2012) · Diabetes Care · doi:10.2337/dc12-s011 · Cited by 2,240 · see citing works
Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease
de Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M. P., Christ‐Schmidt, H., Goldsberry, A., Houser, M. T., Krauth, M., Heerspink, H. J. L., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1306033 · Cited by 1,041 · see citing works
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Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes
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- Authors
- the ADVANCE Collaborative Group
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- the ADVANCE Collaborative Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-06-12
- Volume
- 358
- Issue
- 24
- Pages
- 2560-2572
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W1526927233
- Semantic Scholar
- fe174aa78fe69925b81f3e59a621a1ad0ed0f972
- Cited by
- 7,397
- References
- 28
- Citations by year
- 2026: 137 · 2025: 173 · 2024: 253 · 2023: 279 · 2022: 298 · 2021: 370 · 2020: 398 · 2019: 395 · 2018: 448 · 2017: 453 · 2016: 433 · 2015: 460 · 2014: 523 · 2013: 505 · 2012: 512
- FWCI
- 421.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Griffith Research Online (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- GW Pharmaceuticals
- Novo Nordisk
- Servier
- Medical Research Council
- National Health and Medical Research Council (211086, 358395)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- tight glycemic control, type 2 diabetes, HbA1c, gliclazide, macrovascular events, diabetic nephropathy, diabetic retinopathy, cardiovascular mortality, hypoglycemia, cardiovascular risk reduction, glycemic targets, myocardial infarction, stroke
- MeSH terms
- Aged, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Diabetic Nephropathies, Drug Therapy, Combination, Female, Follow-Up Studies, Gliclazide, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Middle Aged, Risk Factors, Proportional Hazards Models
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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