60th Congress of the German Diabetes Society
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Remission in Prediabetes Reduces Type 2 Risk by 70%. The Key is Normoglycemia, Not Just Weight Loss.
Achieving remission in prediabetes drastically lowers the risk of developing type 2 diabetes. Normalizing blood glucose levels is crucial, while mere weight loss plays a less significant role, explains Professor Dr. Reiner Jumpertz-von Schwartzenberg from the Medical Clinic for Diabetology, Endocrinology, and Nephrology at the University of Tübingen.
Twenty-four years ago, the American Diabetes Prevention Program showed that an intensive lifestyle intervention can reduce diabetes risk by 58%. Even 15 years after randomization, the risk reduction remained at 27%. Currently, recommendations to lose 5-7% of body weight in prediabetes are based on this data.
Recent evaluations of the Tübingen PLIS study involving 1,105 individuals with prediabetes have however nuanced this picture. Among those with at least a 5% weight loss, no significant differences were observed in Body Mass Index (BMI) between responders (normal glucose regulation) and non-responders (prediabetes/type 2 diabetes), but differences were noted in insulin sensitivity and visceral fat reduction.
Significant Risk Reduction Even Without Weight Loss
The diabetes risk for responders decreased by 73%. In the subgroup without weight loss, remission still achieved a risk reduction of 71%. A post-hoc analysis also indicated a lower risk of cardiovascular death, heart failure, and major adverse cardiovascular events. Findings from the Diabetes Prevention Program and a Chinese cohort confirmed these results.
The factors influencing prediabetes were explored by Dr. Sabrina Schlesinger from the German Diabetes Center (DDZ). A meta-analysis of 44 studies involving nearly 15,000 individuals with prediabetes shows a linear relationship between weight loss and risk reduction—both for progression to diabetes and the return to normoglycemia. Evidence supports Mediterranean, low-fat, low-carb, and high-fiber diets, as well as interval fasting and increased intake of unsaturated fatty acids.
Unhealthy Lifestyle Blocks Path to Normoglycemia
Modifiable factors such as obesity, abdominal adiposity, inactivity, and smoking decrease the chances of attaining normoglycemia. Face-to-face interventions and formats combining in-person and digital measures were more effective than purely digital programs involving apps and online coaching. Participants preferred professionally guided structured lifestyle interventions to medication therapy.
In a behavioral study on weight reduction, therapy adherence dropped to around 20% within less than a year, reported Professor Dr. Nikolaos Perakakis from the University Center for Metabolic Diseases at TU Dresden. Metformin lowers diabetes risk, particularly among younger individuals, obese persons, and women with a history of gestational diabetes. However, there is no conclusive evidence for a reduction in diabetes-related complications or mortality rates.
In analyzing data from the STEP 10 study, 81% of obese participants with prediabetes achieved normoglycemia by week 52 under Semaglutide, compared to 14% under placebo. Approximately six months after cessation, 44% of Semaglutide-treated individuals remained within the normal range (versus 18%). In the SURMOUNT-1 trial, the diabetes incidence under Tirzepatide was dose-dependent, ranging from 0.4-1.6% versus 13.3% under placebo.
Semaglutide Protects the Heart Regardless of HbA1c
A post-hoc analysis of the SELECT study indicates a reduction in cardiovascular events with Semaglutide, independent of baseline HbA1c values. Metaanalysis data for SGLT2 inhibitors indicate approximately a 20% risk reduction for heart and kidney failure. The LIFETIME study from the German Center for Diabetes Research (DZD) is currently evaluating Dapagliflozin in the context of prediabetes.
Questions regarding patient selection remain: with a prediabetes prevalence of 10-12%, widespread pharmacotherapy seems unrealistic, stated Professor Perakakis. Stratifications based on HbA1c, obesity, cardiovascular history, selected biomarkers, or subphenotypes are under discussion.
Individuals with prediabetes should be motivated early on to adopt a practical lifestyle change, the speaker concluded. The goal must be normoglycemia, not just weight loss. For high-risk patients, adjunctive pharmacotherapy may gain importance in the future.
