Reviewing Efficacy, Safety of Weight Loss Therapies in T1D

Weight loss therapies may improve health outcomes and provide other benefits to people living with type 1 diabetes (T1D), according to new research published in the journal Current Opinion in Endocrinology, Diabetes and Obesity.¹ However, investigators noted that these therapies have different adverse effects that could impact T1D treatment.

Obesity is a significant public health concern in the US and impacted 41.9% of people in 2020. The prevalence of obesity has also been steadily rising over the past couple of decades. From 1999 through 2020, obesity in the country increased by about 11%.² People with T1D are at an increased risk of developing obesity. In 2021, approximately 28% of people living with T1D also had obesity, highlighting the critical need to focus on treating both conditions.³

“Promising new medications for the treatment of overweight and obesity are now available and have seen a dramatic rise in use; they may also provide weight loss benefits in people living with T1D,” the authors wrote. “Yet dual treatment of obesity and T1D presents its own challenges. Weight loss in T1D may reduce insulin requirements and lead to an increase in hypoglycemia severity and frequency. Other concerns related to weight loss include medication [adverse] effects such as euglycemic diabetic ketoacidosis, cardiovascular disease, and depression.”

Matthew J. Freeby, MD, director of the Gonda Diabetes Center and assistant clinical professor of medicine at the University of California, San Diego, David Geffen School of Medicine, and Kyrstin L. Lane, MD, a general endocrinologist at the Gonda Diabetes Center in Santa Monica, California, conducted a review to evaluate potential risks and benefits of weight loss therapies in patients with concomitant T1D and obesity.

The investigators performed a search of PubMed for studies that assessed clinical outcomes of both approved and off-label medications used to treat T1D. Search terms for the study included medical nutrition therapy obesity type 1 diabetes; exercise obesity type 1 diabetes; metformin type 1 diabetes; and glucagon like peptide-1 [GLP-1] receptor agonist type 1 diabetes. Randomized controlled trials, systematic reviews, and real-world observational studies were included in the review.

Medical nutrition therapy, exercise, and behavioral modifications are often considered the first steps in preventing or treating obesity. The investigators found that the data showed weight loss programs can benefit patients with T1D. Choosing a specific diet was seen to be less impactful than a diet that is sustainable. The data also showed that although exercise had only a modest benefit on weight loss, it provided benefits for cardiovascular and psychological health as well as reduced risk of regaining weight.

When looking at different insulin formulations—such as short- and long-acting formulations—investigators found modest differences in weight gain. In a head-to-head randomized clinical trial included in the review, 549 patients with T1D were given either 300 units/mL of insulin glargine (Gla-300) or 100 units/mL of insulin glargine (Gla-100). The study found that change in hemoglobin A_1c was equivalent between the 2 groups. However, patients who received Gla300 gained 0.6 kg less weight than those who received Gla-100.

The investigators also found that current pharmacologic therapies used to treat weight loss in obesity, such as metformin and GLP-1 receptor agonists, have limited data on efficacy and safety. GLP-1 receptor agonists, which have become extremely popular for weight loss recently, are approved to treat type 2 diabetes and for weight loss. They are not approved to treat T1D, but they have been evaluated for their impact on glucose control, body weight, and adverse effects. A meta-analysis included in the review compared 4 different GLP-1 receptor agonists in 3377 patients. In 17 studies in the meta-analysis, average weight loss was 4.9 kg from liraglutide 1.8 mg, 3.77 kg for liraglutide 1.2 mg, 2.27 kg for liraglutide 0.6 mg, and 4.06 kg for exenatide, all compared with placebo.

“People living with T1D are at risk for the development of obesity due to multiple factors,” the authors concluded. “Similar to the general population, weight loss may improve outcomes in T1D especially as they relate to cardiovascular health, kidney disease, and mortality. Yet treatment does not come without risk, especially with T1D, and they may include hypoglycemia and diabetic ketoacidosis. At this time, more studies across all lines of treatment are needed to evaluate both efficacy and safety.”

READ MORE: Diabetes Resource Center

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References

1. Freeby M, Lane K. Treating obesity in type 1 diabetes mellitus – review of efficacy and safety. Curr Opin Endocrinol Diabetes Obes. 2024;31(1):1-7. doi:10.1097/MED.0000000000000841

2. Stierman B, Afful J, Carroll MD, et al. National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files—Development of Files and Prevalence Estimates for Selected Health Outcomes. National Health Statistics Reports; June 14, 2021. NHSR No. 158. Accessed April 15, 2024. https://stacks.cdc.gov/view/cdc/106273 

3. Kueh MTW, Chew NWS, Al-Ozairi E, le Roux CW. The emergence of obesity in type 1 diabetes. Int J Obes (Lond). 2024;48(3):289-301. doi:10.1038/s41366-023-01429-8