Study summary · research use only
Effects of once-daily oral orforglipron on weight and metabolic markers: a systematic review and meta-analysis of randomized controlled trials
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This meta-analysis of randomized controlled trials in adult human patients examined once-daily oral orforglipron's association with weight and metabolic markers. Four studies comprising 815 patients were included, of whom 620 (76.1%) were prescribed orforglipron. Compared with placebo, orforglipron was associated with reductions in body weight, body mass index, and waist circumference, and with a greater proportion of patients achieving weight loss of ≥ 5%, ≥ 10%, and ≥ 15%. The most common adverse events reported were gastrointestinal. The authors describe orforglipron use as associated with a decrease in body weight compared with placebo, with an increase in non-severe gastrointestinal adverse events, and note phase 3 trials are expected to provide further long-term data.
Abstract
The aim of this study is to assess the effects of once-daily oral orforglipron on weight and metabolic markers in adult patients. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched until February 2024 for randomized controlled trials (RCTs) comparing orforglipron versus placebo or other anti-obesity medications in adult patients. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) or risk differences for binary endpoints were computed, with 95% confidence intervals (CIs). Heterogeneity and risk of bias were assessed with I2 statistics and Rob-2, respectively. Statistical analyses were performed using R, version 4.2.2. A total of four studies were included, comprising 815 patients, of whom 620 (76.1%) were prescribed orforglipron. Compared with placebo, orforglipron reduced body weight (WMD -6.14 kg, 95% CI -9.62 to -2.66 kg), body mass index (WMD -2.87 kg/m2, 95% CI -4.65 to -1.10 kg/m2), and waist circumference (WMD -5.32 cm, 95% CI -9.13 to -1.51 cm). More patients treated with orforglipron than placebo achieved a weight loss of ≥ 5% (RR 3.31, 95% CI 2.23-4.93), ≥ 10% (RR 5.24, 95% CI 2.07-13.31), and ≥ 15% (RR 9.53, 95% CI 1.26-71.89). The most common adverse events were related to the gastrointestinal tract. In this meta-analysis, the use of once-daily oral orforglipron by adult patients was associated with a significant decrease in body weight, as compared with placebo, with an increase in non-severe gastrointestinal adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-daily oral orforglipron over the long term.
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