Background Glucagon-like peptide-1 receptor agonists (GLP1RAs) are relatively newer anti-hyperglycemic agents, which have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus. Design We performed a meta-analysis of randomized controlled trials to evaluate the cardiovascular outcomes of GLP1RAs compared to placebo in type 2 diabetes mellitus patients. We performed an additional subgroup analysis to evaluate the role of GLP1RAs in patients with chronic kidney disease. Methods MEDLINE, Cochrane and ClinicalTrials.gov databases were searched from inception to 15 July 2019. The authors extracted relevant information from articles and independently assessed the study quality. Results Compared to placebo, GLP1RAs demonstrated a significant reduction in all-cause mortality (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.82–0.95; P < 0.001), cardiovascular mortality (OR 0.88, 95% CI 0.81–0.96; P = 0.004), primary composite endpoint (OR 0.86, 95% CI 0.80–0.91; P < 0.001) and non-fatal stroke (OR 0.86, 95% 0.77–0.95; P = 0.004). There was no statistical difference in non-fatal myocardial infarction (OR 0.92, 95% CI 0.83–1.01; P = 0.09). In subgroup analyses of patients with estimated glomerular filtration rate less than 60 ml/min/1.73 m2 and less than 30 ml/min/1.73 m2, there was no significant difference in the primary composite endpoint. Conclusions GLP1RAs demonstrated a significant reduction in all-cause mortality, cardiovascular mortality, primary composite endpoint and non-fatal stroke in patients with type 2 diabetes mellitus. There was no significant difference in the primary composite endpoint in patients with type 2 diabetes mellitus and chronic kidney disease.

Objective To assess the response of serum triglycerides (TG) to continuous insulin infusion (CII) in adults with hypertriglyceridemia-associated acute pancreatitis (HTGP). Methods Retrospective analysis of TG response to standardized CII therapy in 77 adults admitted to intensive care with TG >1000 mg/dL and HTGP. Results Participants had initial TG 3869.0 [2713.5, 5443.5] mg/dL and were 39.3 ± 9.7 years old, 66.2% males, 58.4% Hispanic, BMI 30.2 [27.0, 34.8] kg/m2, 74.0% with diabetes mellitus (DM) and 50.6% with excess alcohol use. TG-goal, defined as ≤1,000 ± 100 mg/dL, was achieved in 95%. Among the 73 TG-goal achievers (responders), 53.4% reached TG-goal in <36 hours after CII initiation (rapid responders). When compared to slow responders taking≥36 hours, rapid responders had lower initial TG (2862.0 [1965.0, 4519.0] vs 4814.5 [3368.8, 6900.0] mg/dL), BMI (29.4 [25.9, 32.8] vs 31.9 [28.2, 38.3] kg/m2), DM prevalence (56.4 vs 94.1%), and reached TG-50% (half of respective initial TG) faster (12.0 [6.0, 17.0] vs 18.5 [13.0, 32.8] hours). Those with DM (n = 57) vs non-DM (n = 20) were obese (31.4 [28.0, 35.6] vs 27.8 [23.6, 30.3] kg/m2), took longer to reach TG-final (41.0 [25.0, 60.5] vs 14.5 [12.5, 25.5] hours) and used more daily insulin (1.7 [1.3, 2.1] vs 1.1 [0.5, 1.9] U/kg/day). Among those with DM, the rapid responders had higher daily use of insulin vs slow responders 1.9 [1.4, 2.3] vs 1.6 [1.1, 1.8] U/kg/day. All results significant. In multivariable analysis, predictors of faster TG response were absence of DM, lower BMI and initial TG. Conclusion CII was effective in reaching TG-goal in 95% of patients with HTGP. Half achieved TG-goal within 36 hours. Presence of DM, higher BMI and initial TG slowed the time to reach TG-goal. These baseline parameters and rate of decline to TG-50% may be real-time indicators to initiate and adjust the CII for quicker response.

Background: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. Methods: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight’s Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200–499 mg/dL), severe (500–999 mg/dL), or very severe (≥1000 mg/dL). Results: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [ P =0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. Conclusions: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.

Dyslipidemia promotes atherosclerosis and causes cardiovascular diseases. Statins are potent lipid-lowering medications with a cardiovascular mortality benefit. They are generally safe and well tolerated but sometimes can be associated with side effects of variable severity. The most common side effect is statin-associated muscle symptoms. Uncommon side effects include new-onset diabetes mellitus and elevation in liver enzymes. These effects can lead to noncompliance and premature discontinuation of the medication. Hence, it is crucial to identify patients with true statin-associated side effects (SASE) to ensure optimal statin use. The appropriate evaluation of the patient before starting statins and proactive utilization of available diagnostic tests to rule out alternate etiologies mimicking adverse effects are essential for accurate diagnosis of SASE. In patients with true SASE, timely intervention with modified statin or non-statins is beneficial. Herein, we discuss key clinical trial data on statins and non-statins, and describe our center’s approach toward patients with SASE.