Metformin may help patients maintain weight loss long-term — ScienceDaily

Does Metformin Cause Weight Loss?

In the Diabetes Prevention Program (DPP) clinical trial and its long-term follow-up study, among the persons who lost at least 5 percent of their body weight during the first year, long-term maintenance of weight loss was more likely if they had been assigned to treatment with metformin than with placebo or lifestyle intervention. Being older and losing a greater amount of weight in the first year were the most consistent predictors of lasting weight loss. Findings from a cohort study are published in Annals of Internal Medicine.

Weight loss plays a central role in efforts to prevent or delay type 2 diabetes. As such, identifying good predictors of long-term weight loss could lead to improved weight management. The DPP was a randomized controlled trial that compared weight loss and diabetes prevention with metformin, intensive lifestyle intervention (ILS), or placebo among more than 3,000 participants with prediabetes, and its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. The DPP/DPPOS is the largest and longest-running study of metformin for prevention of diabetes.

After the first year, twice as many participants in the ILS group versus the metformin group lost at least 5 percent of their body weight. However, those who were assigned to the metformin group had greater success at maintaining their weight loss between years 6 and 15, while patients were still being followed. The researchers noted that greater weight loss at one year predicted long-term weight loss across all groups. Early weight loss was also important with regard to diabetes incidence. The researchers found that cumulative diabetes incidence rates over 15 years were lower among those who lost at least 5 percent of their weight in the first year.

According to the study authors, future research should focus on whether metformin could be a useful intervention for weight loss maintenance after initial weight loss with lifestyle interventions, antiobesity drugs or devices, or bariatric surgery.

Dr. Gadde and his fellow investigators tracked 3,234 people who had obesity or were overweight, and had elevated blood sugar levels. Researchers randomly selected them to receive either metformin, a placebo, or an intensive diet and exercise program.

Those in the lifestyle intervention group completed 16 sessions where they learned how to eat healthful foods, reduce their calorie and fat intake, and develop an exercise regimen incorporating 150 minutes of moderate-intensity physical activity, such as walking, per week.

During the first year, the lifestyle intervention patients lost the most weight. Nearly 63 percent in this group lost at least 5 percent of their weight in the first year compared with 28.5 percent in the metformin group and 13.4 percent in the placebo group.

Yet investigators observed that the highest proportion of those who kept pounds off after 6 to 15 years was in the metformin group. The percentage who maintained more than 5 percent weight loss was 56 percent in the metformin group versus 43 percent in the lifestyle group and 42 percent in the placebo arm.

RELATED: Losing This Much Weight May Put Type 2 Diabetes in Remission, Study Suggests

Kevin M. Pantalone, DO, an endocrinologist at Cleveland Clinic in Twinsburg, Ohio, and the director of clinical research of Cleveland Clinic’s Endocrinology and Metabolism Institute, suspects that the metformin participants had better long-term outcomes than the lifestyle group because taking daily pills may be easier to continue over time compared with dramatic dietary and exercise changes.

“Keeping patients engaged in lifestyle modifications, or other weight loss efforts in general, is challenging in the long term, as enthusiasm wanes, or because the weight loss invariably hits a plateau, and patients can become frustrated and disengage as a result,” says Dr. Pantalone, who was not involved in the study.

He believes that the simultaneous use of medication and lifestyle interventions may produce the best results in the long run.

“Addressing weight loss in the short term and the long term would likely best be accomplished by leveraging as many modalities as possible, and addressing as many variables as possible,” says Pantalone.

“The current follow-up observational report did not include a combined intensive lifestyle intervention (ILS) and metformin intervention group, so we do not know whether the two interventions are additive or synergistic for either initial weight loss or for the long-term maintenance of weight loss.”

RELATED: 6 Foolproof Ways to Lose Weight for Diabetes and Heart Health

A corresponding editorial, also published in April 2019 in the journal Annals of Internal Medicine, recognized additional limitations and factors to consider in evaluating the results.

While the percentage who maintained weight loss at year 15 was greater in the metformin takers, the hard numbers were bigger for the lifestyle intervention participants — 373 versus 172 in the metformin group.

Furthermore, the number of participants in the ILS and placebo groups who received metformin increased over time, wrote editorial authors Leslie Katzel, MD, PhD, and John Sorkin, MD, PhD, with the Baltimore VA Medical Center Geriatric Research Education and Clinical Center and University of Maryland School of Medicine.

Gadde says the study began with participants who were at risk of developing diabetes, so the data cannot be directly applied to treatment of patients with diabetes.

“Nevertheless, when taken together with an enormous amount of data gathered from studies of patients with diabetes, our study data is consistent in that one of the benefits of metformin is a small degree of long-term weight loss,” says Gadde.

In future studies, researchers would like to investigate whether metformin can help maintain weight loss that is initially achieved with diet, weight loss drugs, or bariatric surgery. One question they’d address, for example, is whether people lose weight initially with low-calorie diets and then take metformin for maintaining that weight loss for several years.

No matter what the approach, maintaining a healthy weight is an ongoing and challenging process.

“Obesity is a chronic disease,” says Pantalone, “and it must be managed continuously — just as we manage high blood pressure, diabetes, and high cholesterol — in order to help patients lose weight and maintain that weight loss moving forward.”

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Diabetologia: “Metformin: historical overview,” “Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study,” “Metformin and the gastrointestinal tract.”

American Diabetes Association: “What Are My Options?”

Mayo Clinic: “Metformin revisited.”

Medical Hypotheses: “Metformin exerts anti-obesity effect via gut microbiome modulation in prediabetics: A hypothesis.”

The Journal of Clinical Investigation: “Role of AMP-activated protein kinase in mechanism of metformin action.”

Molecular Endocrinology: “Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action.”

Diabetes Spectrum: “Anti-Diabetes and Anti-Obesity Medications: Effects on Weight in People With Diabetes.”

Current Opinion in Endocrinology, Diabetes and Obesity: “Effects of metformin on weight loss: potential mechanisms.”

Current Obesity Reports: “Metformin: Mechanisms in Human Obesity and Weight Loss.”

Diabetes, Obesity {amp}amp; Metabolism: “Metformin-associated prevention of weight gain in insulin-treated type 2 diabetic patients cannot be explained by decreased energy intake: A post hoc analysis of a randomized placebo-controlled 4.3-year trial.”

World Journal of Diabetes: “Crosstalk between gut microbiota and antidiabetic drug action.”

Diabetes Care: “Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study.”

Annals of Internal Medicine: “Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes.”

American Heart Association: “Lifestyle Changes for Heart Attack Prevention.”

Current Opinion in Clinical Nutrition and Metabolic Care: “Metformin: old friend, new ways of action-implication of the gut microbiome?”

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