More Good News for GLP-1 RA in Type 2 Diabetes

SOURCE: Mann JFE, Ørsted DD, Brown-Frandsen K, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 2017;377:839-848.

Since 2008, the FDA has required all new diabetes medications to provide evidence of cardiovascular (CV) safety. The good news is that several classes of agents have demonstrated not only CV safety, but even efficacy in reducing CV events and (in some cases) all-cause mortality.

The glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide, the sodium-glucose co-transporter-2 inhibitors empagliflozin and canagliflozin, and the dopamine agonist bromocriptine have demonstrated beneficial effects on CV outcomes. Whether these results will be revealed as a class effect remains to be determined.

Alongside the favorable CV data, there is good news in relation to renal endpoints in some of these same trials, the most recent of which is reported from the liraglutide CV safety trial (LEADER). Renal outcomes showed favorable effects of liraglutide compared to placebo, primarily driven by a reduction in the number of patients who developed new macroalbuminuria (> 300 mg urinary albumin/24 hours). Similarly, the rate of decline in renal function, as measured by glomerular filtration rate, was statistically significantly less in patients treated with liraglutide than placebo.

Reductions in microvascular disease (early nephropathy, in the case of type 2 diabetes) has been a major justification for management of glucose for several decades. It is reassuring to confirm that the risk for more advanced nephropathy is ameliorated by use of liraglutide.

Menopausal Hormone Replacement

SOURCE: Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: The Women’s Health Initiative randomized trials. JAMA 2017;318:927-938.

Hormone replacement therapy (HRT) reached its peak in the late 1990s based on observational data that suggested improvements in cardiovascular health, cognition, genitourinary health, and other factors. That changed drastically following the HERS trial and the Women’s Health Initiative (WHI), both of which found not only no cardiovascular benefit associated with HRT but increased adversities such as breast cancer and venous thrombosis.

Women were enrolled in the WHI from 1993-1998, and have been followed through 2014, so clinicians can look at the long-term effects of their treatments for the six or seven years they participated in the trial through that date. There was no difference in all-cause mortality or cancer-related mortality between treated and untreated patients over 18 years of follow-up. It has been noted that younger women (age 50-59 years) in the WHI had a favorable outcome for all-cause mortality during the trial. This trend continued through the 18-year follow-up (hazard ratio for mortality, 0.87; confidence interval, 0.76-1.00).

For women who currently use or have used hormone replacement for menopausal symptoms, these data should be reassuring that their symptom relief does not come at a cost of increased total or cancer-related mortality.

A Link Between Demodex Mites and Rosacea

SOURCE: Chang YS, Huang YC. Role of Demodex mite infestation in rosacea: A systematic review and meta-analysis. J Am Acad Dermatol 2017;77:441-447.e6.

Rosacea is a common dermatologic disorder of uncertain etiology that often is refractory to therapy. Although numerous interventions have been tried, no cure for rosacea is at hand. Antibiotics (e.g., tetracyclines, metronidazole), beta-blockers (e.g., propranolol), alpha-beta-blockers (e.g., carvedilol), systemic steroids, and calcineurin inhibitors (e.g., tacrolimus) have demonstrated some degree of success, but many patients must rely on polypharmacy for adequate symptom control.

An association of the Demodex mite and rosacea has been recognized for more than 50 years. Indeed, antiparasitic medications (ivermectin, permethrin) recently have been shown to produce a favorable effect on rosacea. To better delineate the Demodex-rosacea relationship, Chang and Huang performed a meta-analysis of studies comparing the prevalence of Demodex and the Demodex density (intensity of mite colonization) in patients with rosacea vs. controls. Patients with rosacea were nine times more likely to be infested with Demodex than controls. Similarly, Demodex density was statistically significantly higher in rosacea patients.

The role of Demodex in rosacea appears to be well demonstrated. Since eradication of Demodex is insufficient to resolve rosacea, other pathophysiologic pathways also must be involved.