Studies look at weight loss, suicide risks for GLP-1s
A cohort study found significantly more weight loss in patients taking tirzepatide than semaglutide, while another analysis found no increased risk of suicide with glucagon-like peptide-1 (GLP-1) receptor agonists.
Tirzepatide was associated with significantly greater weight loss than semaglutide in a recent cohort study, while a separate target-trial emulation study looked at whether suicidal thoughts or behaviors were associated with the use of glucagon-like peptide-1 (GLP-1) receptor agonists.
In the first study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using data from a collective of U.S. health care systems. On-treatment weight outcomes were assessed through Nov. 3, 2023. On-treatment weight change was assessed as 5% or greater, 10% or greater, or 15% or greater weight loss and percentage change in weight at three, six, and 12 months. Results were published online July 8 by JAMA Internal Medicine.
Among 18,386 propensity-score matched patients initiating tirzepatide or semaglutide, the mean baseline weight was 110 kg. Follow-up was ended by treatment discontinuation for 5,140 patients (55.9%) receiving tirzepatide and 4,823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss of all degrees (hazard ratios [HRs], 1.76 [95% CI, 1.68 to 1.84], 2.54 [95% CI, 2.37 to 2.73], and 3.24 [95% CI, 2.91 to 3.61] for ≥5%, ≥10%, and ≥15% weight loss, respectively). Patients receiving tirzepatide at three months (difference, −2.4%; 95% CI −2.5% to −2.2%), six months (difference, −4.3%; 95% CI, −4.7% to −4.0%), and 12 months (difference, −6.9%; 95% CI, −7.9% to −5.8%) had greater on-treatment changes in weight. Rates of gastrointestinal adverse events were similar between groups, and consistent results were seen in patients with and without diabetes.
“Future work is needed to compare the effect of tirzepatide and semaglutide on other key end points (eg, reduction in major adverse cardiovascular events),” the study authors wrote.
The second study found no increased risk for suicidal thoughts or behaviors associated with the use of GLP-1 receptor agonists to treat type 2 diabetes. The findings were published July 16 by Annals of Internal Medicine.
Researchers used Medicare data from January 2017 to December 2020 to investigate risk for suicidal ideation and behaviors in older adults with type 2 diabetes taking GLP-1 receptor agonists versus sodium-glucose cotransporter-2 (SGLT-2) inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors. The data included patients ages 66 years and older who had type 2 diabetes, had no record of suicidal ideation at baseline, and were starting treatment.
In the 21,807 pairs of patients treated with a GLP-1 receptor agonist versus an SGLT-2 inhibitor, the hazard ratio for suicidal ideation and behaviors was 1.07 (95% CI, 0.80 to 1.45), for a rate difference of 0.16 per 1,000 person-years (95% CI, −0.53 to 0.86). In the 21,402 pairs of patients treated with a GLP-1 receptor agonist versus a DPP-4 inhibitor, the hazard ratio was 0.94 (95% CI, 0.71 to 1.24), for a rate difference of −0.18 per 1,000 person-years (95% CI, −0.92 to 0.57).
The study authors concluded that there was no clear increased risk for suicidal ideation and behaviors with GLP-1 receptor agonists, “although estimates were imprecise and a modest adverse risk could not be ruled out.”