10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study

Probably not a substantial claim: may not pass S3 (load-bearing).

The Swedish Obese Subjects Study's non-surgical group averaged a 0.1% weight gain at 10 years.

“For example, in the non-surgical treatment group of the Swedish Obese Subjects Study21 of bariatric surgery, a 0·1% weight gain was reported, on average, after 10 years.”

• cites [21] Sjöström, 2004, Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery, N Engl J Med sourceDisputed

  The Abstract reports a 0.1% weight gain in the control group after two years, not ten. At ten years, it reports a 1.6% weight gain in that group. (LLM, conf=0.95)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Earlier extrapolation from DPP incidence estimated median diabetes delay at 11 years for lifestyle and 3 years for metformin.

“The delay in median time to diabetes diagnosis was previously estimated to be 11 years for the lifestyle and 3 years for the metformin groups on the basis of extrapolation of DPP incidence.19”

• cites [19] 2005, The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance, Ann Intern Med sourceSupported

May combine two claims.

The metformin arm lost about 2.5 kg on average during DPP and kept most of that loss.

“The metformin group lost a mean of 2·5 kg during DPP and maintained most of that weight loss.”

May combine two claims.

The lifestyle group subsequently regained about 1 kg, while metformin and placebo groups initially lost and then regained weight back to DPPOS baseline levels.

“The lifestyle group subsequently regained about 1 kg, whereas the metformin and placebo groups initially lost and then regained weight back to their respective levels at DPPOS baseline (figure 2).”

May combine two claims.

The largest lifestyle benefit appeared in those aged 60-85 at randomisation (49% lower rate), a group where metformin showed no significant effect.

“The lifestyle effect was greatest in participants aged 60–85 years at randomisation (49% rate reduction), in whom metformin had no significant effect (figure 3).”

May combine two claims.

The metformin and lifestyle arms had lower HbA1c and fasting glucose than the original placebo arm, even though more placebo participants took antidiabetic drugs.

“HbA1c and fasting glucose concentrations were lower in the metformin and lifestyle groups than in the original placebo group, despite more people in the placebo group using antidiabetic drugs than those in the metformin (excluding study-assigned metformin) or lifestyle groups.”

May combine two claims.

Over the whole follow-up, the lifestyle arm had lower systolic and diastolic blood pressure and triglycerides than the other arms, despite less anti-hypertensive use.

“Averaged over all follow-up, systolic and diastolic blood pressure and triglycerides were lower in the lifestyle than in the other groups, although use of anti-hypertensive drugs was less frequent.”

May combine two claims.

Lifestyle group participants initially lost the most weight (mean 7 kg by 1 year), gradually regained, but still weighed about 2 kg less than at randomisation.

“The lifestyle group participants initially lost the most weight (a mean of 7 kg by 1 year), but gradually regained, although still weighing about 2 kg less than they did at randomisation.”

May combine two claims.

During the 10-year follow-up since DPP randomisation, the original lifestyle group lost weight and then partly regained it, while the modest weight loss in the metformin group was maintained.

“During the 10·0-year (IQR 9·0–10·5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained.”

May combine two claims.

Over the 10 years after DPP randomisation, the lifestyle arm had a 34% lower diabetes incidence and the metformin arm an 18% lower incidence than placebo.

“Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24–42) in the lifestyle group and 18% (7–28) in the metformin group compared with placebo.”

• Also stated in: § Results · plain

  “During the combined DPP, bridge, and DPPOS periods, the incidence rate of the lifestyle group was reduced by 34% (95% CI 24–42) and metformin by 18% (7–28) compared with placebo.”

May combine two claims.

During DPPOS, cumulative incidence curves for the 1994 participants without diabetes on Sept 1, 2002 did not continue to separate as in DPP, because additional cases were similar across groups.

“During this study, cumulative incidence curves for the 1994 participants who remained without diabetes on Sept 1, 2002, (five of the original 1999 had no follow-up) did not continue to separate as they had in DPP, because the accumulation of additional cases of diabetes was similar in the three groups (figure 3).”

May combine two claims.

During the DPP, diabetes incidence rates were 4.8 per 100 person-years in the intensive lifestyle group, 7.8 in the metformin group, and 11.0 in the placebo group.

“Diabetes incidence rates during the DPP were 4·8 cases per 100 person-years (95% CI 4·1–5·7) in the intensive lifestyle intervention group, 7·8 (6·8–8·8) in the metformin group, and 11·0 (9·8–12·3) in the placebo group.”

May combine two claims.

At the most recent yearly examination, 23% of lifestyle, 19% of metformin, and 19% of placebo participants had become normoglycaemic by previously defined criteria.

“At the most recent yearly examination, 23% in the lifestyle, 19% in the metformin, and 19% of participants in the placebo groups had become normoglycaemic by criteria defined and reported previously (fasting glucose <6·1 mmol/L, 2-h glucose <7·8 mmol/L, and no previous diagnosis of diabetes).4,5”

May combine two claims.

During DPPOS, the lifestyle arm's incidence rate stayed flat, while the placebo and metformin arms' rates declined.

“Incidence rates were stable in the lifestyle group, but fell in the placebo and metformin groups during the DPPOS.”

May combine two claims.

Across the study, the lifestyle arm had lower systolic and diastolic blood pressure and triglycerides than metformin and placebo, but these differences disappeared by the end of follow-up.

“Overall, systolic and diastolic blood pressure and triglycerides were lower in the lifestyle than in the metformin and placebo groups, but these differences were not maintained by the end of follow-up (table 4).”

May combine two claims. The quote only partly states this claim.

The median delay to onset of diabetes was about 4 years for lifestyle and 2 years for metformin compared with placebo, estimated from time to 40% cumulative incidence.

“This point was delayed by about 4 years by lifestyle and 2 years by metformin, compared with placebo.”

• Also stated in: § Discussion · plain

  “In this study, onset of diabetes was delayed by about 4 years by lifestyle intervention and 2 years by metformin compared with placebo.”

May combine two claims.

Lifestyle intervention also improved blood pressure and lipids, even though participants' own physicians prescribed fewer drugs.

“The lifestyle intervention also resulted in improved blood pressure and lipid concentrations despite a reduction in drug treatment prescribed by participants’ personal physicians.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

BOOST attendance in the original lifestyle arm averaged 17% (19% among those without diabetes) and rose with age.

“Attendance at BOOST sessions for the original lifestyle group averaged 17% (19% for participants without diabetes), and was positively associated with age.”

May combine two claims.

During the bridge, the metformin and placebo arms attended lifestyle sessions more than the original lifestyle arm and lost modest weight, though less than the lifestyle arm had during DPP.

“The two groups newly exposed to lifestyle intervention (metformin and placebo) had higher attendance than did the lifestyle group during the bridge period, and they achieved modest weight loss, although less than the lifestyle group did during the DPP.8”

May combine two claims.

During follow-up after DPP, diabetes incidence in the former placebo and metformin groups fell to equal that in the former lifestyle group, but cumulative diabetes incidence remained lowest in the lifestyle group.

“During follow-up after DPP, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group.”

May combine two claims.

In DPPOS, among non-diabetic metformin participants, 57% took at least 80% of the prescribed dose and 70% took some metformin; outside-study metformin use was 1% in the lifestyle arm and 3% in the original placebo arm.

“During DPPOS, 57% of the non-diabetic metformin participants took 80% or more of the prescribed metformin dose and 70% took metformin in any amount, compared with 1% of non-diabetic participants in the lifestyle group and 3% in the original placebo group who took metformin prescribed outside the study.”

May combine two claims.

DPPOS enrolment was similar by sex and ethnic origin, but was lower among women with prior gestational diabetes and higher among those who already had diabetes by Sept 1, 2002.

“Enrolment into this follow-up study from the DPP cohort did not differ significantly by sex or ethnic origin, but was lower in women with a history of gestational diabetes than in those without and higher in participants who had developed diabetes by Sept 1, 2002, than in those without diabetes (table 1).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The DPPOS analysis adjusted for baseline values in analyses of change.

“Each analysis of change from the start of DPPOS was adjusted for the study’s baseline value, and each analysis of change from DPP randomisation until the analysis closing date was adjusted for the DPP baseline value.”

May combine two claims.

Higher age, HbA1c, and cholesterol, and in women lower weight and BMI, were associated with enrolment.

“Enrolment was also related to greater age, HbA1c, cholesterol concentrations, and in women, by lower weight and body-mass index (webappendix p 1).”

May combine two claims.

Lifestyle intervention or metformin can keep diabetes from developing or delay it for at least a decade.

“Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years.”

• Also stated in: § Discussion · boosted

  “Our results have shown that a reduction in diabetes cumulative incidence by either lifestyle intervention or metformin therapy persists for at least 10 years.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Three pair-wise comparisons of diabetes incidence were done, each at an alpha of 0.017.

“We did three pair-wise comparisons of diabetes incidence in the three intervention groups, each at an α of 0·017—ie, the conventional 0·05 adjusted for three comparisons.”

May combine two claims.

DPPOS enrolled 2766 of 3150 eligible DPP participants (88%); the median additional follow-up was 5.7 years.

“2766 of 3150 (88%) enrolled for a median additional follow-up of 5·7 years (IQR 5·5–5·8).”

Classified as probably not a substantial claim.

The DPPOS analysis was by intention-to-treat.

“Analysis was by intention-to-treat.”

• Also stated in: § Statistical analysis · plain

  “The intention-to-treat analysis compared each intervention with placebo on a modified product-limit life-table distribution with a log-rank test statistic.”

May combine two claims.

In the DPP randomized trial, over an average of 2.8 years, the intensive lifestyle arm lowered diabetes incidence by 58% and the metformin arm by 31%, relative to placebo, among high-risk adults.

“diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo.”

• Also stated in: § Participants · plain

  “lifestyle intervention reduced incidence of diabetes by 58% and metformin by 31% compared with placebo during an average of 2·8 years in the DPP.4”

• cites [4] 2002, Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, N Engl J Med sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Treatment assignment was double-blind for the metformin and placebo arms.

“The metformin and placebo groups were masked (double blind) to treatment.3,4,6”

May combine two claims.

HELP session attendance averaged 18% in the original lifestyle arm, 15% in metformin, and 14% in placebo (20%, 15%, and 14% among non-diabetic participants).

“Attendance at quarterly lifestyle sessions (HELP) averaged 18% for the original lifestyle group, 15% for the metformin group, and 14% for the placebo group (20%, 15%, and 14%, respectively, in non-diabetic participants).”

May combine two claims.

Both lifestyle and metformin produced weight loss that lasted 10 years.

“Lifestyle and metformin interventions succeeded in producing long-term (10-year) weight loss.”

May combine two claims.

Limitations of the present analyses include less than complete enrolment and treatment modifications after the end of DPP.

“Limitations of the present analyses include the less than complete enrolment in our study and the treatment modifications after the end of DPP.”

May combine two claims.

The convergence of diabetes incidence across arms during bridge and DPPOS could stem from a weaker lifestyle effect in the original lifestyle arm than during DPP, from giving group lifestyle intervention to the placebo and metformin arms, or from both.

“Therefore, convergence of diabetes incidence rates in the three treatment groups during the bridge and DPPOS might be a result of either a diminished effect of the lifestyle intervention for the original lifestyle group compared with the intensive lifestyle intervention during the DPP, or the introduction of group-implemented lifestyle intervention to the DPP placebo and metformin groups, or both.”

May combine two claims.

Current delay estimates are shorter than the earlier ones, mainly because placebo-arm diabetes incidence fell.

“The present estimated delays are smaller than the original estimates owing largely to the reduction in diabetes incidence in the placebo group.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Shifts in how diabetes was ascertained over time make interpretation harder.

“However, the change in ascertainment of diabetes over time complicates data interpretation.”

May combine two claims.

The absence of a DPPOS incidence difference did not come from a rebound in the lifestyle arm; instead, placebo and metformin incidence fell to match the lifestyle rate, which stayed largely unchanged.

“This finding was not attributable to a rebound effect in the lifestyle group but to a fall in incidence in the placebo and metformin groups that resulted in similar rates as achieved by lifestyle intervention, which changed little throughout follow-up (table 3 and figure 4).”

May combine two claims.

At 10 years after DPP randomisation, the lifestyle and metformin arms still had lower cumulative diabetes incidence than placebo, even though treatments changed after an average of 3.2 years.

“10 years after DPP randomisation, cumulative incidence of diabetes remained lower in the lifestyle and metformin groups than in the placebo group, despite changes in treatments after a mean of 3·2 years.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The cumulative data overlap the separately reported periods, add no statistical information, and do not come from a single predesigned intervention, so tests or CIs for the whole post-randomisation period need cautious interpretation.

“Cumulative data are completely contained within the other separately reported periods, statistically provide no additional information, and do not represent a predesigned uniform intervention over time. Therefore, significance tests or CIs reported for the entire time since randomisation should be interpreted cautiously.”

May combine two claims.

The Da Qing trial in 577 Chinese people with impaired glucose tolerance found 6-year cumulative diabetes rates of 68% with usual care, 48% with diet, 41% with exercise, and 46% with diet plus exercise; all three interventions were similarly effective.

“After 6 years of treatment, cumulative diabetes incidences were high (68% in usual care, 48% in diet, 41% in exercise, and 46% in diet plus exercise groups), with all three interventions being similarly effective.”

• cites [12] Pan, 1997, Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and Diabetes Study, Diabetes Care sourceNot checked — no full text of the source
• cites [26] Li, 2008, The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study, Lancet sourceNot checked — no full text of the source

May combine two claims.

In that Finnish study, the intervention was not delivered during the 3-year follow-up but still cut incidence by 39%.

“Although the intervention was not actively delivered during the 3-year follow-up, it remained effective with a 39% reduction in incidence.18”

• cites [18] Lindström, 2006, Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study, Lancet sourceNot checked — no full text of the source

May combine two claims.

These factors probably contributed to greater weight loss and protection from diabetes in older than in younger participants, particularly in the lifestyle group.

“These factors probably contributed to greater weight loss (figure 2) and protection from diabetes in the older than in the younger participants, particularly in the lifestyle group (figure 3).”

May combine two claims.

Complications were too rare to analyse treatment effects; the complete DPPOS follow-up is needed to see whether preventing or delaying diabetes also affects complications.

“However, diabetes complications were too infrequent for analysis of treatment effects, and the full DPPOS follow-up will be needed to assess whether prevention or delay of diabetes onset will have the same effect on complications.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The authors know of no published long-term follow-up of drug intervention to prevent diabetes other than DPPOS.

“As far as we know, no long-term follow-up of drug intervention to prevent diabetes has been published except for the DPPOS.”

May combine two claims.

The hypothesis that incidence rates in former placebo and metformin groups fell because most susceptible participants developed diabetes during DPP is not supported by stability of diabetes incidence in the lifestyle group, by findings in high-risk Pima Indians, or by results of the Finnish Diabetes Prevention Study.

“However, this hypothesis is not supported by stability over time of diabetes incidence in the lifestyle group, by findings in high-risk Pima Indians, in whom the yearly incidence of diabetes in people with impaired glucose tolerance increased rather than decreased during a 10-year follow-up,17 or by results of the Finnish Diabetes Prevention Study18 in which diabetes incidence in the control group”

• cites [17] Saad, 1988, The natural history of impaired glucose tolerance in the Pima Indians, N Engl J Med sourceNot checked — no full text of the source
• cites [18] Lindström, 2006, Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study, Lancet sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

Since diabetes is defined by arbitrary glycaemic thresholds, stopping hyperglycaemia from worsening prevents or postpones diabetes onset.

“Because diabetes is defined by somewhat arbitrary cut-off points of hyperglycaemia, arrest of progression of hyperglycaemia prevents or delays onset of diabetes.”