I am happy to contribute to the editorial by Lisa Eramo published in Medical Economics, January 2018. The article is important as it raises physician awareness of Merit-based Incentive Payment System (MIPS) under which hypertension management falls. MIPS, part of 2015 MACRA, will go into effect in 2019.
GT
This meta-analysis of four major clinical trials (ELIXA, LEADER, SUSTAIN 6, EXSCEL) reveals safety of GLP-1 agonists, bur more importantly their cardiovascular benefits on mortality, myocardial infarction and stroke in adults with type 2 diabetes.
The next natural step would be the quest for oral version of GLP-1 agonist given its positive profile on appetite, glucagon, insulin, glucose metabolism, proteinuria and cardiovascular system.
GT
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.
GT
Patients with type 2 diabetes receiving Invokana experienced 30% and 20% lower rates of kidney disease progression and cardiovascular events respectively, when compared to the placebo group.
Results were so obvious and significant that the study was terminated early. About 4500 subjects with DM2 were followed for about 2.5 years. No increased rates of fractures or amputations were seen with Invokana.
GT
The Endocrine Society has just released its guidelines on how to manage the elderly with diabetes. Guidelines are overall similar to those of ADA and AACE but with greater emphasis in avoidance of adverse events such; as hypoglycemia, malnutrition, excessive weight loss, frailty, falls, and drug side effects. See below for more details.
GT
AACE standards were published in January 2019. They are a continual update of the original 2013 guidelines. Unlike ADA which recommends a general A1c target ≤7.0%, AACE promotes a tighter A1c goal of ≤6.5% for most patients with type 2 diabetes.
Recommendations also address lifestyle interventions, obesity, prediabetes, hypoglycemia, hypertension and dyslipidemia. Oral and injectable medications including insulin are discussed. A key priority is the avoidance of hypoglycemia — do no harm!
GT
Results of ELLIPSE trial are of major significance as they show that Victoza addition to Metformin helps in further reduction of A1c and fasting plasma glucose. The efficacy and safety appear to be similar as in adults. The most common side effects are gastrointestinal in nature. Based on ELLIPSE trial outcomes, I anticipate broadening of FDA indications for Victoza, to include children and adolescents
GT
This major observational study shows that the tight control of risk factors is associated with much lower rates of cardiovascular events and total mortality in patient with type 1 diabetes. Such factors are hyperglycemia, systolic blood pressure, protein in the urine, and the “bad” cholesterol (A1c, sBP, McAlb, LDLc).
This association has already been seen in adults with type 2 diabetes. For a practitioner, this study calls for a tight control of the above risk factors in patients with type 1 diabetes as in those with type 2. A group of 30,000 DM1 individuals were followed for about 10 years
GT
This simple study shows that frozen red raspberries in quantities of 125-250 mg (1-2 cups), when taken with a typical high-carb breakfast, improve insulin resistance in adults with prediabetes. Although these results would need to be validated, having red raspberries for breakfast sounds just right.
GT
This short phase 2 clinical trial shows that the oral insulin 338 improves fasting plasma glucose similar to the long-acting insulin glargine. Hypoglycemia rates are also similar. However, further studies of the oral insulin 338 are halted due to its need for high doses and cost. A group of 50 patients were followed for 8 weeks. The quest for the first oral insulin, nonetheless, continues.
GT
Clinical experience has consistently shown that addition of a GLP-1 agonist to a SGLT2 inhibitor improves hyperglycemia in patients with uncontrolled diabetes. Current study SUSTAIN 9 proves just that for semaglutide, a once weekly injectable GLP-1 agonist.
Addition of semaglutide reduced A1c by 1.4% and bodyweight by 8.4 lbs. Results were statistically significant. As expected, the GI side effects were more pronounced with semaglutide. About 72% of patients were also taking metformin and 13% sulfonylurea.
A group of 300 participants were followed for 30 weeks.
GT
Jardiance shows positive outcomes in African American adults. It reduces the A1c by 0.8%, body weight by 2.7 pounds and more interestingly the systolic blood pressure by 8 mmHg, similar to a standard blood pressure medication.
A group of 150 African American participants were randomized to receive Jardiance 25 mg daily or placebo for 6-months.
The SGLT2 inhibitor would be a great choice for patients with concomitant hyperglycemia and systolic hypertension.
GT
About 80,000 diabetes patients were analyzed from 8 clinical trials.
Authors found that GLP1 agonists and SGLT2 inhibitors prevented cardiovascular events (MACE) equally by 14% in those with established CVD. However, both classes of medications did not appear to be effective in reducing MACE in adults with diabetes but without established CVD.
SGLT2 inhibitors showed superior results compared to GLP1 agonists in regard to preventing hospitalizations for heart failure or severe kidney disease progression, such as end-stage-renal disease or death.
If cost, side effects, drug interactions and contraindications allow, diabetes patients would greatly benefit from these therapies on three fronts; glucose control, heart and kidney disease prevention.
GT
For diabetes patients, practical recommendations would be:
Start moderate-intensity statin therapy if:
Young, age 20-39, with microvascular complications or long-standing DM.
Older, age 40-75, without major risk factors.
Start high-intensity statin ± ezetimibe if the following factors are present with the goal of reducing LDLc ≥50%:
Multiple risk factors
ASCVD 10YR ≥20%
For adults >75, clinician-patient discussion is needed if statin were to be started or continued.
GT
Among patients with type 2 diabetes initiating second-line diabetes therapy, the short-term cardiovascular outcomes of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors were similar.
Higher cardiovascular risk was associated with use of sulfonylureas or basal insulin compared with newer drug classes.
Clinicians may consider prescribing GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors more routinely after metformin rather than sulfonylureas or basal insulin.
JAMA
Patients with diabetes mellitus are at increased risk for bone fragility fracture secondary to multiple mechanisms.
Hyperglycemia can induce true dilutional hyponatremia. Hyponatremia is associated with gait instability, osteoporosis, and increased falls and bone fractures, and studies suggest that compromised bone quality with hyponatremia may be independent of plasma osmolality.
Analyses of this research support the hypothesis that hyponatremia is an additional risk factor for osteoporosis and fragility fracture among patients with diabetes mellitus.
JES
This major observational study suggests that statins reduce the risk of diabetic neuropathy, diabetic foot ulcers, and more importantly the risk of diabetic retinopathy. Risk reduction ranges from 10% to 45%. This could be due to statin-induced decreased microvascular inflammation. About 38,000 patients were followed for 7.5 years.
GT
The automated insulin pump has already shown great results in type 1 diabetes in an ambulatory setting. This study shows that it is as useful in type 2 diabetes patients treated in the hospital. Patients utilizing the “artificial pancreas” had better glycemic control, without an increased risk of hypoglycemia. I anticipate that closed-loop, automated insulin devices will become the “standard of care” for hospitalized patients with type 1 and type 2 diabetes in the future.
GT
Old drug, new approach. Verapamil has classically been used to treat hypertension and cardiac arrhythmias. This randomized phase 2 clinical trial shows a novel use of the drug by improving pancreatic beta cell function in recently diagnosed type 1 diabetes. Verapamil helped patients use lower doses of insulin as well as experiencing less hypoglycemia. These are exciting and promising results.
GT
