Skill Checkup: A 36-Year-Old Man With Type 2 Diabetes Is Struggling to Lose Weight

Anne L. Peters, MD


June 01, 2022

The weight loss observed in individuals taking SGLT2 inhibitor monotherapy is moderate because of counterregulatory mechanisms striving to maintain body weight. For this reason, SGLT2 inhibitors in combination with agents acting via decreased food intake (eg, GLP-1 RAs) have been investigated. In fact, in DURATION-8, a 28-week randomized controlled trial, investigators examined the efficacy and safety of combination therapy with dapagliflozin and exenatide once per week in type 2 diabetes that is inadequately controlled by metformin. There were significantly greater reductions in absolute weight change with exenatide plus dapagliflozin (-3.31 kg) compared with exenatide (-1.51 kg) or dapagliflozin (-2.28 kg) alone.

More recently, the AWARD-10 study demonstrated greater weight loss with the sequential addition of dulaglutide 1.5 mg to patients treated with an SGLT2 inhibitor (with or without metformin).

Finally, a meta-analysis of eight randomized controlled trials with a total of 1895 patients conducted from 2018 through 2021 showed that GLP-1 RA–SGLT2 inhibitor combination therapy led to a much more significant reduction in glycemic levels (including A1c, FPG, and 2-hour plasma glucose) than monotherapy. In addition, combination therapy was associated with significant reductions in body weight, body mass index, and systolic blood pressure. Nevertheless, with the extension of the follow-up, these therapeutic efficacies weakened.

SGLT2 inhibitors and GLP-1 RAs are already frequently used concomitantly in clinical practice, and in the future, use of the combination will probably increase.

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