Efficacy and Safety of Liraglutide 3.0 mg in Patients with Overweight and Obese with or without Diabetes: A Systematic Review and Meta-Analysis

Abstract

Background. Liraglutide in a 3.0 mg subcutaneous dose daily is approved for weight reduction. Objectives. Objectives are to evaluate the efficacy and safety of liraglutide 3.0 mg in patients with overweight and obesity irrespective of diabetic status. Methods. We conducted an electronic database search in PubMed, Embase, and https://ClinicalTrial.gov to identify all randomized control trials (RCTs) that evaluated the efficacy and safety of liraglutide 3.0 mg dose compared to placebo in overweight (≥27 kg/m2) and obese (≥30 kg/m2) patients above 18 years of age. Results. We compared the pooled estimate of the study results between liraglutide 3.0 mg groups and placebo groups both in diabetic and nondiabetic patients. The efficacy outcomes that were found to be significant among respective studies involving nondiabetic patients vs. diabetic patients were mean change in body weight from baseline: 12 studies [MD = −5.04 kg (95% CI = −5.60, −4.49), P < 0.001 , I2 = 92.95%] vs. 2 studies [MD = −4.14 kg (95% CI = −4.95, −3.32), P < 0.001 , I2 = 0%], reduction in waist circumference from baseline: 8 studies [MD = −3.64 cm (95% CI = −4.43, −2.85), P < 0.001 , I2 = 96.5%] vs. 2 studies [MD = −3.11 cm (95% CI = −3.88, −2.34), P < 0.001 , I2 = 0%], BMI reduction from baseline: 5 studies [MD = −1.95 kg/m2 (95% CI = −2.22, −1.68) vs. 1 study [MD = −1.86 kg/m2 (95% CI = −2.14, −1.57), P < 0.001 , I2 = 0%, P < 0.001 , I2 = 95.6%], proportion of patients losing more than 5% of weight loss from baseline: 8 studies [RR = 2.21, (95% CI = 1.89, 2.58), P = 0.03 , I2 = 59.02%] vs. 2 studies [RR = 2.34, (95% CI = 1.93, 2.85), P = 0.39 , I2 = 0.00%], and 10% weight loss from baseline: 7 studies [RR = 3.36, (95% CI = 1.92, 5.91), P = 0.00 , I2 = 87.03%] vs. 2 studies [RR = 3.64, (95% CI = 2.46, 5.40), P = 0.81 , I2 = 0.00%]. Safety outcome assessment with use of liraglutide 3.0 mg compared with placebo in respective nondiabetic vs. diabetic patients revealed significant proportion of patients experiencing the adverse events: 9 studies [RR = 1.11, (95% CI = 1.04, 1.18), P = 0.00 I2 = 79.15%] vs. 2 studies [RR = 1.06, (95% CI = 1.01, 1.11), P = 0.42 , I2 = 0.03%] but similar risk of serious adverse events: 9 studies [RR = 1.03, (95% CI = 0.70, 1.51), P = 0.26 , I2 = 18.54%] vs. 2 studies [RR = 1.11, (95% CI = 0.67, 1.84), P = 0.25 , I2 = 23.77%] and TDAEs: 4 studies [RR = 0.89, (95% CI = 0.35, 2.28), P = 0.03 , I2 = 61.89%] vs. 1 study [RR = 2.53, (95% CI = 1.00, 6.37)]. However, the pooled estimates irrespective of the glycaemic status were mean change in body weight from baseline: 14 RCT [MD = −4.91 kg (95% CI = −5.43, −4.39), P < 0.001 , I2 = 92.35%], reduction in waist circumference from baseline: 10 studies [MD = −3.55 cm, (95% CI = −4.21, −2.89), P < 0.001 , I2 = 94.99%], BMI reduction from baseline: 6 studies [MD = −1.86 kg/m2, (95% CI = −2.14, −1.57), P < 0.001 , I2 = 96.14%], and proportion of patients losing more than 5% and 10% of weight from baseline: [RR = 2.23, (95% CI = 1.98, 2.52), P < 0.001 , I2 = 48.87%] and [RR = 3.28, (95% CI = 2.23, 4.83), P < 0.001 , I2 = 78.98%], respectively. Also, the proportion of patients experiencing the adverse event was more with liraglutide 3.0 mg compared with placebo 11 study [RR = 1.09, (95% CI = 1.04, 1.15), P < 0.01 , I2 = 76.60%] and similar risk for both serious adverse events: 11 studies [RR = 1.09, (95% CI = 1.04, 1.15), P < 0.01 , I2 = 76.60%] and TDAEs: 5 studies [RR = 1.14, (95% CI = 0.50, 2.60), P < 0.01 , I2 = 64.93%] with liraglutide compared with placebo. Conclusions. Liraglutide in 3.0 mg subcutaneous dose demonstrated significant weight reduction with a reasonable safety profile for patients with overweight or obesity regardless of diabetic status compared to placebo.

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“…More importantly, once-weekly semaglutide increased the weight loss of at least 10% (53% more) and 15% (33% more) compared with placebo. The significant numbers were notably higher than those observed in previous studies involving other anti-obesity medications within a similar patient population [35,36].…”

Efficacy and safety of tirzepatide in overweight or obese adults without diabetes: systematic review and meta-analysis of randomized controlled trials

“…Liraglutide also led to a signi cant reduction in body weight (MD: -5.04 kg), BMI (MD: -1.95 kg/m 2 ), and waist circumference (MD: -3.64 cm), with a higher percentage of participants achieving 5% and 10% weight loss [13].…”

Obesity vs. Metabolically Healthy Obesity in East Asia

“…Chronic cardiovascular and cerebrovascular conditions are thought to be caused by the synergistic effect of diabetes or prediabetes with hypertension on forming calcified arterial plaques, especially in the coronary and cerebral arteries [12,13]. This metabolismdisease relationship is proven by reports that mortality risks decrease observably upon loss of fat from the central trunk [14][15][16][17]. Furthermore, studies of glucose-controlling drugs that result in smaller waistline circumference and large population studies have observed decreased odds ratios of diabetic and cardiovascular risks after moderate weight loss [14,18].…”