Larger HbA1c drop in type 2 diabetes treated with semaglutide vs. other GLP-1 agents
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Key takeaways:
- Semaglutide was associated with a larger reduction in HbA1c and body weight than other GLP-1 receptor agonists.
- Treatment discontinuation due to gastrointestinal adverse events was more common with semaglutide.
Semaglutide conferred greater reductions in HbA1c and body weight among adults with type 2 diabetes than other GLP-1 receptor agonists, according to findings from a systematic review and meta-analysis.
“Semaglutide seems to be more efficacious compared with the rest of commercially available GLP-1 receptor agonists, in terms of improvement in glycemia and other cardiometabolic risk factors, among individuals with type 2 diabetes,” Dimitrios Patoulias, MD, MSc, PhD, FRCP, FNSCOPE, an internal medicine physician in the outpatient department of cardiometabolic medicine, second department of cardiology at Aristotle University of Thessaloniki, General Hospital in Greece, and colleagues wrote in a study published in the Journal of Diabetes and Its Complications. “However, it is also associated with significantly greater odds for treatment discontinuation, due to gastrointestinal adverse events, mainly nausea and vomiting.”
Researchers searched the PubMed and Cochrane Library databases up until Feb. 8, 2023, for phase 3 randomized controlled trials comparing the effects of semaglutide (Ozempic, Rybelsus; Novo Nordisk) with other GLP-1 receptor agonists among adults with type 2 diabetes. Trials assessed at least one cardiometabolic parameter and had a minimum duration of 12 weeks. The primary outcome was the HbA1c change with semaglutide compared with other GLP-1s. Change in body weight, BMI and other cardiometabolic parameters were also assessed.
Five randomized controlled trials were included in the study with a total of 3,760 participants. One trial compared once-weekly subcutaneous semaglutide with once-weekly subcutaneous exenatide extended release (Byetta, AstraZeneca), one compared once-weekly subcutaneous semaglutide with once-daily liraglutide (Saxenda, Novo Nordisk), a third compared once-daily oral semaglutide with liraglutide, another trial compared once-weekly subcutaneous semaglutide with once-weekly subcutaneous dulaglutide (Trulicity, Eli Lilly) and the fifth compared once-daily oral semaglutide with dulaglutide.
Adults receiving semaglutide had a greater reduction in HbA1c (mean difference, –0.44%; 95% CI, –0.63 to –0.25; P < .00001) and fasting plasma glucose (mean difference, –0.48 mmol/L; 95% CI, –0.8 to –0.15; P = .004) compared with other GLP-1 agents. Those receiving semaglutide were more likely to achieve an HbA1c of less than 7% (OR = 2.1; 95% CI, 1.4-3.14; P = .003) or an HbA1c of less than 6.5% (OR = 2.16; 95% CI, 1.52-3.07; P < .0001) than adults using other agents.
The semaglutide group had a greater reduction in body weight (mean difference, –2.53 kg; 95% CI, –3.31 to –1.75; P < .00001) and BMI (mean difference, –0.91 kg/m2; 95% CI, –1.18 to –0.63; P < .0001) than those using other agents. Adults receiving semaglutide were more likely to lose 5% or more body weight (OR = 3.7; 95% CI, 2.71-5.06; P < .00001) and 10% or more body weight (OR = 4.39; 95% CI, 3.27-5.9; P < .00001) than those using other GLP-1 receptor agonists.
Semaglutide was associated with greater reductions in waist circumference (mean difference, –2.04 cm; 95% CI, –2.49 to –1.6; P < .00001), systolic blood pressure (mean difference, –1.2 mm Hg; 95% CI, –2.05 to –0.34; P = .006) and diastolic BP (mean difference, –0.67 mm Hg; 95% CI, –1.18 to –0.16; P = .01) compared with other GLP-1 agents. No differences were observed with other cardiometabolic parameters.
Adults receiving semaglutide were more likely to report nausea (OR = 1.43; 95% CI, 1.08-1.88; P = .01) and vomiting (OR = 1.49; 95% CI, 1.1-2.01; P = .01) than those receiving other GLP-1 agents. Treatment discontinuation due to gastrointestinal adverse events was more likely with semaglutide than with other agents (OR = 1.48; 95% CI, 1.15-1.91; P = .002).
“Generated results from relevant randomized controlled trials should be incorporated into daily clinical practice, by amending treatment algorithms used by involved physicians and proposing appropriate treatment combinations, especially for subjects with concomitant cardiorenal disease,” the researchers wrote. “The impact of semaglutide compared with other GLP-1 receptor agonists on surrogate endpoints, including all-cause mortality and CV morbidity and mortality ... remains unclear and should be the focus of future randomized controlled trials.”
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