Efficacy Studies of Semaglutide for Type 2 Diabetes Mellitus

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This article ran in conjunction with the article, "Can Semaglutide Help in Psychiatry Too? Research Shows Promise for AD and PD."

One meta-analysis that included data from 6 placebo-controlled and 7 active-controlled studies using subcutaneous semaglutide found that when compared with placebo, subcutaneous semaglutide 0.5 mg and 1 mg reduced hemoglobin A_1c (HbA_1c) by 1.01% and 1.38%, respectively.¹ The investigators also found that both doses of semaglutide demonstrated superior glycemic efficacy (percentage reduction in HbA_1c, weighted mean difference [WMD], −0.63% [0.5 mg] and −0.84% [1 mg] respectively) compared with other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide, and insulin glargine. Both doses of semaglutide also caused weight loss (WMD, −2.32 kg [0.5 mg] and −4.11 kg [1 mg], respectively), when compared with placebo. Additionally, semaglutide caused more weight loss (WMD, −2.28 kg [0.5 mg] and −3.78 kg [1 mg]) compared with other antidiabetic agents. Semaglutide also did not increase the incidence of any hypoglycemic episodes (OR, 1.11 [0.5 mg]; OR, 1.09 [1 mg]) when compared with placebo. The results were also similar for semaglutide (OR, 0.52 [0.5 mg]; OR, 0.72 [1 mg]) compared with other antidiabetic agents. Compared with placebo or other antidiabetic agents, treatment with semaglutide was associated with increased incidence of nausea, vomiting, and diarrhea.

In a more recent meta-analysis, investigators evaluated the efficacy and safety of oral semaglutide 7 mg and 14 mg among individuals with type 2 diabetes mellitus.² The investigators included data from 11 randomized controlled trials. They found that compared with placebo, semaglutide 7 mg and 14 mg reduced HbA_1c by 1.06% and 1.10%, respectively. Additionally, compared with other antidiabetic agents, semaglutide 7 mg and 14 mg reduced HbA_1c by 0.26% and 0.38%, respectively. Compared with placebo, treatment with oral semaglutide 7 mg and 14 mg reduced body weight by 1.18 kg and 2.96 kg, respectively. Compared with other antidiabetic agents, treatment with oral semaglutide 7 mg and 14 mg reduced body weight by 1.47 kg and 1.78 kg, respectively. Hypoglycemic episodes were not significantly different between the semaglutide 7-mg and 14-mg dosing or placebo. This was also true for both doses of semaglutide compared with other antidiabetic agents. Compared with placebo, oral semaglutide 7 mg showed no significant difference in risk of adverse effects. Oral semaglutide 14 mg had a greater risk of adverse events (nausea, diarrhea, vomiting, decreased appetite, nasopharyngitis, and headache) compared with placebo. Compared with other antidiabetic agents, both doses of semaglutide did not demonstrate any significant difference in the risk of adverse events.

Dr Joshi is a geriatric psychiatrist at Banner Alzheimer’s Institute and assistant clinical professor at University of Arizona College of Medicine-Phoenix. Dr Tampi is professor and chairman of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives Health Behavioral Health Services in Omaha, Nebraska. He is also an adjunct professor of psychiatry at Yale School of Medicine, New Haven, Connecticut.

References

1. Andreadis P, Karagiannis T, Malandris K, et al. Semaglutide for type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(9):2255-2263.

2. Li A, Su X, Hu S, Wang Y. Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2023;198:110605.