Clinical Briefs By Louis Kuritzky, MD
Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.
Male pattern baldness treated with oral dutasteride
Source: Eun HC, et al. Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss. J Am Acad Dermatol 2010;63:252-258.
More than three-fourths of men have some degree of male pattern hair loss by age 70. The unwanted hair loss seen in male pattern hair loss is stimulated by dihydrotestosterone. Clinical trials of low-dose oral finasteride (Propecia® 1 mg/d) have shown that blockade of 5-alpha-reductase (5AR), the enzyme responsible for converting testosterone to dihydrotestosterone, is effective for producing new hair growth.
There are two different 5AR enzymes: Type 1 5AR functions primarily in skin, and type 2 5AR is expressed predominantly in hair follicles and the prostate. Finasteride only blocks type 2 5AR, whereas dutasteride blocks both type 1 and type 2 5AR. The potential utility of dutasteride as a treatment for male pattern hair loss is bolstered by data from large, long-term clinical BPH and prostate cancer trials that demonstrate excellent tolerability.
Eun et al performed a randomized, double-blind, placebo-controlled, 6-month trial in adult men (n = 153) of dutasteride 0.5 mg/d for male pattern hair loss. At the end of the trial, hair counts were statistically significantly improved in the active treatment group, with more than 70% of men self-assessing hair growth to be improved. The safety profile of dutasteride was excellent, with no serious drug-related adverse events.
Theoretically, dutasteride might provide better hair growth results than finasteride because the dual blockade mechanism of the former produces lower DHT plasma levels. Since both agents block type 2 5AR, which is thought to be the primary culprit in male pattern hair loss, and there are no comparison trials between finasteride and dutasteride, it remains uncertain which treatment is superior.
Which is better: COX2 or NSAID plus PPI?
Source: Chan FK, et al. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR). Lancet 2010;376:173-179.
The gi toxicity of nsaids is well recognized, with a 1998 report suggesting that as many as 16,500 deaths that year were attributable to NSAID-induced GI bleeding. One of the reputed benefits of the development of cyclo-oxygenase selective NSAIDs was the belief that their relative lack of effect on COX1 would obviate much of the GI toxicity seen. Some patients will continue to use maintenance therapy with anti-inflammatory agents for protracted periods; hence, determination of which GI protection technique is most beneficial is a critical issue. To that end, Chan et al studied Helicobacter-negative patients with osteoarthritis and/or rheumatoid arthritis (n = 4484) to compare GI adverse events (the primary outcome) seen with celecoxib vs a traditional NSAID (diclofenac) plus PPI (omeprazole). Utilization of aspirin was a study exclusion.
At 180 days, the celecoxib group showed a statistically significantly lesser GI event rate than the diclofenac plus omeprazole group (0.9 % vs 3.8%). Tolerability, as measured by treatment discontinuation, of celecoxib (200 mg bid) was superior to diclofenac 75 mg bid plus omeprazole 20 mg qd (6% vs 8%).
For patients requiring maintenance anti-inflammatory treatment, GI consequences of celecoxib are fewer than if a traditional NSAID is combined with a proton pump inhibitor, although cost considerations may preclude universal application of this preferred treatment.
Comparing insulin and incretins
Source: Horton ES, et al. Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care 2010;33:1759-1765.
The general electric centricity research database contains EMR information on more than half a million adults with DM2. Of course, therapeutic choices for DM2 vary widely among this large population. Because the incretin class of medications (DPP4 inhibitors and GLP-1 agonists) has been associated with weight loss (or at least weight neutrality), the resultant changes in CV risk factors usually seen with weight reduction could ultimately influence CV outcomes. Horton et al studied CV biomarkers (BP, lipids) and markers of glycemic control in subjects that had received incretins and compared these same markers in subjects treated with insulin. All subjects (total n = 44,539) had to be treated for at least 1 year.
Exenatide, the only GLP-1 agonist available at the time this study was reported, was associated with a 3 kg weight loss, compared to a 1.1 kg weight loss for the sitagliptin group and a 0.6 kg weight gain for the insulin group. SBP improved in all 3 groups, but only very slightly (1-2 mmHg). LDL improved modestly in all three groups (5%-6% reduction). The absolute reduction in A1c was greater with insulin (1.0% A1c reduction) than incretins (0.5% A1c reduction); however, the baseline A1c was higher in the insulin group (8.8%) vs the incretin group (7.7%).
Similar improvements in SBP, LDL, and A1c were seen in this database. Whether the more advantageous impact on weight seen with incretins will ultimately impact CV outcomes remains to be determined.
More than three-fourths of men have some degree of male pattern hair loss by age 70. The unwanted hair loss seen in male pattern hair loss is stimulated by dihydrotestosterone.Subscribe Now for Access
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