Combining two diabetes medications helps with weight loss

Rockville, Maryland (August 20, 2024) – New research shows that a combination of drugs improves weight loss, glucose control and insulin resistance better than either drug alone. Combining two diabetes drugs, such as semaglutide like Ozempic or Rybelsus, with a second, newer class of drugs could provide a noninvasive solution to help people with type 2 diabetes lose weight. It could also help them manage their disease without the need for bariatric surgery. The study appears in advance in American Journal of Physiology-Endocrinology and Metabolism and was elected as APSchoose Articles for August.

Type 2 diabetes and obesity, especially when they occur together, carry the long-term risk of cardiovascular disease. Studies have shown that losing at least 15% of a person's body weight can improve metabolic factors associated with diabetes and reduce associated health risks. Drugs such as semaglutide, which contain glucagon-like peptide-1 receptor agonists (GLP-1 analogs), lower blood sugar levels on their own. However, researchers are exploring newer treatments that combine different classes of drugs to improve weight loss and obesity-related conditions in people with type 2 diabetes. One of these additional classes of drugs is called dual amylin and calcitonin receptor agonists, or DACRAs.

In a new study, researchers from Denmark examined a rat model of obesity and diabetes. For seven months, adult rats were treated with either semaglutide alone, a DACRA called KBP-336 alone, or a combination of the two drugs. During the first three months of the study, all treatment groups lost a significant amount of weight. However, during the second half of the study, the combination group experienced more sustained and persistent weight loss than the single-drug treatment groups. The animals that received the combination therapy also had less visceral fat. Visceral fat can be particularly dangerous because it surrounds organs and can interfere with their function.

The research team found that the newer drug KBP-336 stabilized fasting blood sugar levels both alone and in combination with semaglutide. It also reduced endotrophin – a product derived from collagen found in fat tissue. High endotrophin levels can be a sign of heart and liver failure. The combination therapy also provided a measure of glucose tolerance and lower insulin levels than either drug alone.

“In obesity and type 2 diabetes, the treatment gap between pharmacotherapies and bariatric surgery is narrowing, but to definitively close it, combination therapies are needed,” the researchers wrote. “Overall, KBP-336 is a promising candidate for the treatment of obesity and type 2 diabetes, both alone and in combination with GLP-1 analogues.”

Read the full article “Sustained metabolic improvement by combining dual amylin and calcitonin receptor agonists and semaglutide treatments in a rat model of obesity and diabetes.” It is highlighted as one of this month’s “Best of the Best” at the American Physiological Society’s APSchoose Program. Read this month's selected research articles.

NOTE FOR JOURNALISTS: To arrange an interview with a member of the research team, please contact APS Media Relationships or call 301.634.7314. For more research highlights, see our Press release.

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