Obesity rates are rising worldwide. Acute pancreatitis is also on the rise. The authors of the current study followed prospectively about 120,000 individuals. As expected, they found a high correlation between BMI and acute pancreatitis events. Investigators also observed that hypertriglyceridemia could explain about 22-30% of the relationship between obesity and pancreatitis.
The results of the study, although not new, confirm prior research and knowledge that obesity leads to insulin resistance, which in turn elevates blood triglyceride concentration. Hypertriglyceridemia is a well-known specific cause of acute pancreatitis, especially when triglyceride measurements are above 500 mg/dL.
Clinically, it is essential to screen obesity patients for hypertriglyceridemia. A fasting lipid panel is a simple and inexpensive laboratory test that can provide significant insights into the patient’s risk of insulin resistance and pancreatitis.
The Lancets, Diabetes and Endocrinology has just published the results of SUSTAIN 8 clinical trial. The study compared the efficacy and safety of semaglutide 1.0 mg/week versus canagliflozin 300 mg/day in patients with uncontrolled diabetes taking only metformin.
Investigators recruited and followed a group of 800 adults with baseline A1c 7.0-10.5% from 111 centers in 11 countries. They found that the addition of semaglutide to metformin lowered A1c and body weight more than canagliflozin by 0.5% and 2.2 lbs respectively. The trial observed that patients receiving semaglutide experienced higher rates of nausea, while those taking canagliflozin developed more urinary tract infections.
Current ADA and AACE guidelines recommend the use of a GLP-1 agonist or SGLT-2 inhibitor after metformin in uncontrolled type 2 diabetes. Although the study did not compare GLP-1 agonists and SGLT-2 inhibitors as a class, it did suggest initiation of semaglutide 1.0 mg/week over SGLT-2 inhibitors. SGLT-2 inhibitors are regarded to be clinically similar.
An SGLT-2 inhibitor, however, would be a better second-line agent after metformin in diabetes patients with clinical or subclinical heart failure but with proper kidney function (eGFR >45). I anticipate that ADA and AACE guidelines will incorporate SUSTAIN 8 results in their next published standards.
The New England Journal of Medicine first published the results of the HPS2-THRIVE randomized clinical trial in 2014. Niacin addition to statin therapy did not improve cardiovascular outcomes. Instead, the trial found an increased rate of adverse events.
Last month, Clinical Therapeutics published a detailed analysis of the trial’s adverse events. Authors found that niacin addition significantly increased the risk of new-onset diabetes, worsening of diabetes, severe bleeding, and serious infections by about 30%, 55%, 40%, and 20% respectively.
The above adverse outcomes were more pronounced in the first year after the start of niacin. The infection rate was an exception, which stayed elevated throughout the trial. Investigators followed and analyzed a group of 25,000 patients with high baseline risk for the vascular disease over four years.
Based on HPS2-THRIVE data, it is difficult to justify the clinical use of niacin from the cardiovascular standpoint.
The major randomized clinical trial, ASCEND, shows that aspirin 100 mg daily lowers the rates of cardiovascular events by 12% in patients with diabetes but increases the risk of bleeding by 30%.
A group of 15,000 participants with diabetes but without baseline CVD were followed for about 7 years.
Case by case clinical judgment would be key in evaluating CVD benefits vs. bleeding risks of aspirin use in patients with diabetes.
The current study is of a major clinical significance as it shows that EPA lowers ischemic cardiovascular events by 25% in high rick CVD patients who are already receiving statin therapy. The EPA treated patients, however, experienced more hospitalizations for atrial fibrillation and a higher propensity for serious bleeding than placebo. Findings are remarkable as they come from a major randomized clinical trial (REDUCE IT). About 8,000 patients were followed for 5 years.
This outcome data is in accordance with established observation and notion that hypertriglyceridemia is an independent risk factor for cardiovascular disease, mainly via increased inflammation and concentration of the non-HDL cholesterol. Prior clinical studies have also shown that EPA lowers non-HDL cholesterol more than DHA.
Omega-3s, EPA and DHA, are two key ingredients of fish oil. A stable and pure form of EPA has been FDA approved for very high serum triglyceride >500 mg/dL since 2012. It is marketed under the brand-name vascepa. Lovaza, a mixture of EPA and DHA, has also been approved by FDA since 2004 for severe hypertriglyceridemia.
I anticipate that in the future NLA, ACC/AHA, AACE and ADA guidelines will reflect and incorporate the current findings of REDUCE IT.
FDA has now approved the first subcutaneous testosterone auto-injector pen (Xyosted) for symptomatic patients with low testosterone levels. It is self-administered once weekly. It comes in three doses, 50 mg, 75, and 100 mg. Recommended starting dose is 75 mg per week. It can increase blood pressure, thus caution is advised in patients predisposed to hypertension and those at increased risk for cardiovascular events. Patients need to be monitor carefully after its initiation. Xyosted is not approved for women or males younger than age 18.
Patients with low testosterone levels could have decreased libido, erections and stamina. They could also suffer from reduced bone mass, muscle mass, and physical capacity. Intramuscular testosterone injection is an efficient and safe way to help patients with testosterone deficiency. The following video shows how to self-administer the testosterone injection.
In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls.
Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls.
Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group.
Trulicity is a GLP-1 receptor agonist. It increases intracellular cAMP in beta cells leading to glucose-dependent insulin release. It also decreases glucagon secretion and slows gastric emptying.
Trulicity is supplied as a solution for subcutaneous injection. The recommended initiating dose is 0.75 mg once weekly. The maximum recommended dose is 1.5 mg once weekly. Administered once weekly, any time of day, with or without food. Trulicity should be injected subcutaneously in the abdomen, thigh, or upper arm.
Victoza was approved by FDA in January 2010. It is an injectable form of GLP-1 analog. It improves diabetes via several mechanisms; insulin sensitivity, appetite suppression, reduced gastrointestinal motility, lower glucagon and higher insulin release in response to food.
A nice video summary by NEJM regarding cardiovascular safety of semaglutide. Semaglutide was approved by the FDA in December 2017. It is a weekly GLP-1 agonist with hyperglycemic and weight loss benefits while safe from cardiac standpoint.