SGLT2 x DPP-4

MONDAY, March 3, 2025 -- Glucagon-like peptide-1 (GLP-1) receptor agonists are not associated with an increased risk for suicidality compared with dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors in adjusted analyses, according to a study published online Feb. 26 in The BMJ . Samantha B. Shapiro, from the Jewish General Hospital in Montreal, and colleagues conducted an active comparator, new user cohort study to examine whether use of GLP-1 receptor agonists is associated with an increased risk for suicidal ideation, self-harm, and suicide compared with DPP-4 inhibitor or SGLT-2 inhibitor use. The first cohort included 36,082 GLP-1 receptor agonist users and 234,028 DPP-4 inhibitor users, and the second cohort included 32,336 GLP-1 receptor agonist users and 96,212 SGLT-2 inhibitor users. In crude analyses, the researchers found an increased incidence of suicidality with GLP-1 receptor agonist versus DPP-4 inhibitor use (crude incidence rates, 3.9 versus 1.8 per 1,000 person-years; hazard ratio, 2.08; 95 percent confidence interval, 1.83 to 2.36). After accounting for confounding factors, this estimate decreased to a null value (hazard ratio, 1.02; 95 percent confidence interval, 0.85 to 1.23). GLP-1 receptor agonist use was also associated with an increased risk for suicidality compared with SGLT-2 inhibitor use (crude incidence rates, 4.3 versus 2.7 per 1,000 person-years; hazard ratio, 1.60; 95 percent confidence interval, 1.37 to 1.87), but the correlation did not persist after accounting for confounding factors (hazard ratio, 0.91; 95 percent confidence interval, 0.73 to 1.12). When suicidal ideation, self-harm, and suicide were analyzed separately in both cohorts, the findings were similar. "These findings should provide some reassurance with respect to the psychiatric safety of these drugs," the authors write. Several authors disclosed ties to the pharmaceutical industry. Abstract/Full Text Editorial Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

FRIDAY, Feb. 28, 2025 -- GLP-1 drugs like Ozempic/Wegovy don’t increase a person’s risk of suicidal actions or thoughts, a new study has concluded. Earlier research had potentially linked these drugs -- which are used to treat type 2 diabetes and obesity -- with suicidal thoughts and self-harm, researchers added. But the new study found no such association after following more than 68,000 diabetics prescribed GLP-1 drugs for a year or more, according to a report in The BMJ . “GLP-1 receptor agonist use was not associated with an increased risk of suicidal ideation, self-harm, or suicide” compared against two other classes of diabetes medications, wrote the research team led by senior researcher Laurent Azoulay , an associate professor of epidemiology and biostatistics at McGill University in Montreal. “These findings should provide some reassurance with respect to the psychiatric safety of these drugs,” researchers concluded. GLP-1 drugs have become wildly popular as weight-loss medications, but with their increased use has come concern over the long-term safety of this class of drugs. For the study, researchers analyzed U.K. data on people with type 2 diabetes who had been prescribed medications for their condition. Glucagon-like peptide-1 (GLP-1) drugs mimic the GLP-1 hormone, which helps control insulin and blood sugar levels, decreases appetite and slows digestion of food. The most prominent of these drugs is semaglutide , which is sold under the name Ozempic for diabetes management and under the name Wegovy for weight loss. In one arm of the study, researchers compared more than 36,000 people prescribed a GLP-1 drug against more than 234,000 patients taking DPP-4 inhibitors for their diabetes between 2007 and 2020. In the second arm, the team compared more than 32,000 GLP-1 patients against more than 96,000 patients taking SGLT-2 inhibitors between 2013 and 2020. All groups were monitored for suicidality -- suicidal thoughts, self-harm or death by suicide. Use of GLP-1 drugs was not associated with an increased risk of suicidality compared to either DPP-4 inhibitors or SGLT-2 inhibitors, results show. “We did not observe associations even among patients with a history of psychiatric disorders, such as self-harm, suicidal ideation, and depression,” the team concluded. Researchers noted that because this was an observational study, it can’t completely rule out a link between GLP-1 drugs and suicide. However, they argued that they controlled for many potential sources of bias. These results also mirror those from GLP-1 clinical trials, which found no additional risk of suicide, researchers noted. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

TUESDAY, Feb. 11, 2025 -- Age differences are seen in the efficacy of treatments for type 2 diabetes , according to a study published online Feb. 3 in the Journal of the American Medical Association . Peter Hanlon, Ph.D., from the University of Glasgow in the United Kingdom, and colleagues reviewed the literature to examine whether age or sex is associated with differences in the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors. Individual participant data were obtained for 103 trials: 103 reported hemoglobin A1c (HbA1c), and six reported major adverse cardiovascular events (MACEs). The researchers found that compared with placebo, SGLT2 inhibitor use was associated with less HbA1c lowering with increasing age for monotherapy, dual therapy, and triple therapy (absolute reductions, 0.24, 0.17, and 0.25 percent, respectively, per 30-year increment in age). GLP-1 receptor agonist use was associated with greater HbA1c lowering with increasing age for monotherapy and dual therapy (absolute reductions, –0.18 and –0.24 percent) but not for triple therapy. Slightly better HbA1c lowering was seen in association with DPP4 inhibitor use in older people for dual therapy (absolute reduction, –0.09 percent) but not for monotherapy or triple therapy. The relative reduction in MACEs with SGLT2 use was greater in older versus younger participants, while the relative reduction with GLP-1 receptor agonist use was less in older versus younger participants. Sex was not associated with differences in efficacy for any of the diabetes treatments studied. "For hemoglobin A1c, use of SGLT2 inhibitors showed modestly reduced efficacy with increasing age," the authors write. "In contrast, the reduction in major adverse cardiovascular events with SGLT2 inhibitors was greater in older people compared with younger people." Several authors disclosed ties to the pharmaceutical industry.