The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies. We performed a systematic search of the PubMed, Embase, and Cochrane Library databases until 31 July 2019, and retrieved all cardiovascular outcome trials (CVOTs) of IBTs conducted for ≥12 months that reported the pre-specified and or pre-adjudicated pancreatitis outcomes. Subsequently, we conducted a meta-analysis to study the risk of AP observed with IBT in CVOTs. A meta-analysis of seven CVOTs of GLP-1 receptor agonists (GLP-1RAs) compared with placebo (N = 55,932) found no significant increase in AP (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.77–1.42; p = 0.77). In contrast, meta-analysis of five CVOTs comparing DPP-4 inhibitors with placebo (N = 47,714) and six CVOTs comparing DPP-4 inhibitors with placebo or active comparator (N = 53,747), found a significant increase (OR, 1.81; 95% CI, 1.21–2.70; p = 0.04 and OR, 1.54; 95% CI, 1.08–2.18; p = 0.02, respectively) in AP without any significant heterogeneity. This meta-analysis revealed a significant association between pancreatitis and DPP-4 inhibitors; however, no such association was observed for GLP-1RAs.

Background: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin. Research design and methods: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs. Results: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ∆ −3.076 Kg; 95% CI, −3.49 to −2.66; P < 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo. Conclusions: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache.

Background: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin. Research design and methods: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs. Results: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ∆ −3.076 Kg; 95% CI, −3.49 to −2.66; P < 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo. Conclusions: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache.

The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies. We performed a systematic search of the PubMed, Embase, and Cochrane Library databases until 31 July 2019, and retrieved all cardiovascular outcome trials (CVOTs) of IBTs conducted for ≥12 months that reported the pre-specified and or pre-adjudicated pancreatitis outcomes. Subsequently, we conducted a meta-analysis to study the risk of AP observed with IBT in CVOTs. A meta-analysis of seven CVOTs of GLP-1 receptor agonists (GLP-1RAs) compared with placebo (N = 55,932) found no significant increase in AP (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.77–1.42; p = 0.77). In contrast, meta-analysis of five CVOTs comparing DPP-4 inhibitors with placebo (N = 47,714) and six CVOTs comparing DPP-4 inhibitors with placebo or active comparator (N = 53,747), found a significant increase (OR, 1.81; 95% CI, 1.21–2.70; p = 0.04 and OR, 1.54; 95% CI, 1.08–2.18; p = 0.02, respectively) in AP without any significant heterogeneity. This meta-analysis revealed a significant association between pancreatitis and DPP-4 inhibitors; however, no such association was observed for GLP-1RAs.

Introduction: Obesity poses a significant increase in morbidity and mortality and thus five anti-obesity drugs have been approved currently by US FDA. Several phase 3 trials have shown a significant improvement in cardio-metabolic profile including significant weight reduction with these agents compared to placebo. Areas covered: We systematically searched the database of PubMed, Embase, The Cochrane Library and The ClinicalTrials.gov up to 30 September 2019 and retrieved all the randomized controlled trials (RCTs) that were conducted with these five drugs for ≥1 year and explicitly reported their efficacy versus placebo. Subsequently, we have conducted the meta-analysis to primarily study the effect of these anti-obesity drugs on weight reduction. We additionally reviewed the effect of these drugs on other cardio-metabolic parameters including key adverse events. Expert opinion: This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ∆ −3.07 Kg, 95% CI, −3.76 to −2.37), phentermine plus topiramate (N = 2985; ∆ −9.77 Kg; 95% CI, −11.73 to −7.81), lorcaserin (N = 16,856; ∆ −3.08 Kg; 95% CI, –3.49 to –2.66), naltrexone plus bupropion (N = 3239; ∆ −4.39 Kg; 95% CI, −5.05 to −3.72) and liraglutide (N = 4978; ∆ −5.25 Kg; 95% CI, −6.17 to −4.32), compared to placebo (all p < 0.00001).

Introduction: Heart failure (HF) in type 2 diabetes mellitus (T2DM) poses a significant increase in mortality. Until recently, anti-diabetic drugs have not been shown to reduce hospitalization due to heart failure (hHF). While thiazolidinedione class and saxagliptin has shown a significantly increased risk, sodium-glucose linked co-transporter 2 inhibitors (SGLT-2Is) have demonstrated a significant reduction in the risk of hHF. Areas covered: We systematically searched the database of PubMed, Embase, ClinicalTrials.gov, and International conference presentation up to 25 December 2018 and retrieved all the studies that were conducted for ≥24 weeks and explicitly reported hHF outcome. Subsequently, we conducted the meta-analysis to study the effect of SGLT-2Is on hHF outcome in randomized controlled trials (RCTs), observational studies, and both. Expert opinion: The meta-analysis of RCTs (N = 34,322), observational studies (N = 15,36,339), and both (N = 15,70,661) demonstrated a significant decrease in hHF (OR 0.70, 0.64, 0.66, respectively, all p = 0.000) with SGLT-2Is compared to placebo or other anti-diabetes drugs in T2DM. A significant benefit in hHF (OR 0.68, p = 0.000) is also observed in patients with established HF (N = 3891) in sub-group meta-analysis of RCTs. Ongoing dedicated HF trials will further enlighten the merits of SGLT-2Is in patients with established heart failure (preserved or reduced) with or without T2DM.

Introduction: Heart failure (HF) in type 2 diabetes mellitus (T2DM) poses a significant increase in mortality. Until recently, anti-diabetic drugs have not been shown to reduce hospitalization due to heart failure (hHF). While thiazolidinedione class and saxagliptin has shown a significantly increased risk, sodium-glucose linked co-transporter 2 inhibitors (SGLT-2Is) have demonstrated a significant reduction in the risk of hHF. Areas covered: We systematically searched the database of PubMed, Embase, ClinicalTrials.gov, and International conference presentation up to 25 December 2018 and retrieved all the studies that were conducted for ≥24 weeks and explicitly reported hHF outcome. Subsequently, we conducted the meta-analysis to study the effect of SGLT-2Is on hHF outcome in randomized controlled trials (RCTs), observational studies, and both. Expert opinion: The meta-analysis of RCTs (N = 34,322), observational studies (N = 15,36,339), and both (N = 15,70,661) demonstrated a significant decrease in hHF (OR 0.70, 0.64, 0.66, respectively, all p = 0.000) with SGLT-2Is compared to placebo or other anti-diabetes drugs in T2DM. A significant benefit in hHF (OR 0.68, p = 0.000) is also observed in patients with established HF (N = 3891) in sub-group meta-analysis of RCTs. Ongoing dedicated HF trials will further enlighten the merits of SGLT-2Is in patients with established heart failure (preserved or reduced) with or without T2DM.

Introduction: Obesity poses a significant increase in morbidity and mortality and thus five anti-obesity drugs have been approved currently by US FDA. Several phase 3 trials have shown a significant improvement in cardio-metabolic profile including significant weight reduction with these agents compared to placebo. Areas covered: We systematically searched the database of PubMed, Embase, The Cochrane Library and The ClinicalTrials.gov up to 30 September 2019 and retrieved all the randomized controlled trials (RCTs) that were conducted with these five drugs for ≥1 year and explicitly reported their efficacy versus placebo. Subsequently, we have conducted the meta-analysis to primarily study the effect of these anti-obesity drugs on weight reduction. We additionally reviewed the effect of these drugs on other cardio-metabolic parameters including key adverse events. Expert opinion: This meta-analysis finds a significant reduction in body weight with orlistat (N = 10,435; ∆ −3.07 Kg, 95% CI, −3.76 to −2.37), phentermine plus topiramate (N = 2985; ∆ −9.77 Kg; 95% CI, −11.73 to −7.81), lorcaserin (N = 16,856; ∆ −3.08 Kg; 95% CI, –3.49 to –2.66), naltrexone plus bupropion (N = 3239; ∆ −4.39 Kg; 95% CI, −5.05 to −3.72) and liraglutide (N = 4978; ∆ −5.25 Kg; 95% CI, −6.17 to −4.32), compared to placebo (all p < 0.00001).

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