Jun 23, 2017


The story

Like supervising first day interns, keeping up with new diabetes meds can leave your head spinning with worry that you've overlooked something important. We've got you covered with the latest on SGLT-2 inhibitors and heart disease.

The background

2015's EMPA-REG OUTCOME surprised many when it found substantial cardiovascular benefits for patients with type II diabetes treated with empagliflozin (Jardiance). The drug is part of a class of oral anti-diabetic agents called sodium-glucose 2 (SGLT-2) inhibitors, which lower blood glucose by promoting increased glucose excretion in the kidneys. Many wondered if the benefits were specific to empagliflozin or part of a broader medication class effect.

The study

CANVAS followed 10,000 patients with type 2 diabetes and an elevated risk of cardiovascular disease for a median follow-up of almost 4 years. Treatment with the SGLT-2 inhibitor canagliflozin (Invokana) reduced a composite outcome of cardiovascular events – cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke – by 14% relative to placebo. The observed benefits were similar in magnitude to those seen with empagliflozin, though unlike EMPA-REG, CANVAS included patients with cardiovascular risk, not just known cardiovascular disease. In an unexpected red flag, canagliflozin produced an increased risk of toe or metatarsal amputation, an adverse effect previously not associated with SGLT-2 inhibitors.

The takeaway

Cardioprotective benefits appear to be a class effect for SGLT-2 inhibitors, so consider adding the meds to metformin for diabetes patients with CV risk factors in need of tighter glucose control. In our clinic, matching these meds to covering insurance plans has been tricky.

Say it on rounds

When your freshly cleaned white coat has a freshly spilled coffee stain 

You’re no stranger to sadness, so consider the plight of those with postpartum depression. Few therapies address the condition even though it affects up to 20% of new mothers. A blinded phase II study of 20 women with severe postpartum depression found that continuous infusion of brexanolone produced substantive reductions in depression severity index scores relative to placebo at 30 days. The drug targets GABAA receptors, which are activated throughout pregnancy but become dysregulated when hormone levels normalize after delivery.

When the jacked consult resident gets way too mad at you

There are all kinds of benefits to reducing unnecessary steroid use. An RCT of 220 patients with severe asthma and eosinophilia found that injections of benralizumab, a monoclonal antibody that targets the IL-5 receptor to induce depletion of eosinophils, reduced oral glucocorticoid requirements by an average of 75% relative to placebo. Half of the patients in the treatment group were able to be taken off of steroids entirely, and benralizumab significantly decreased rates of acute asthma exacerbation.

When your back aches after falling asleep during multi-disciplinary rounds

The effect may be more than physical. A cohort study of over 10,000 elderly adults found that chronic pain was associated with a 9% faster decline in memory and cognitive function over a period of 10 years. Compared to their pain-free counterparts, pain sufferers showed significant impairment in managing medications and personal finances. The authors hypothesize that the mental stress of chronic pain depletes thinking capacity that would otherwise be used to encode memory.
JAMA Int Med

Brush up

Chronic kidney disease

Add diabetes to hypertension to account for roughly 75% of the 20 million adults with chronic kidney disease (CKD) in the United States. Patients are at severe risk for progression to end-stage renal disease and death from cardiovascular causes. Treatment remains ineffective: blood pressure control, the predominant treatment for CKD, delays CKD progression but does not restore glomerular function. Traditional cardiovascular risk factor controls like reducing serum cholesterol and quitting smoking are less effective in CKD patients than in the general population.

Get meta

With intensive blood pressure control and CKD. An analysis of 9 trials with 8,000 total CKD patients found that while intensive (< 130/80 mm Hg) blood pressure control did not delay progression of CKD relative to standard (< 140/80 mm Hg) blood pressure control, there was a trend towards benefit in nonblack patients and those with high levels of proteinuria. Dizziness was the only side effect seen with intensive blood pressure control.

What your running club friends are talking about

Shout out to Gabriele Grunewald, who's moving from daily chemotherapy to competing in the US 1,500-meter track championship. She's locked in battle #4 with adenoid cystic carcinoma.

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