Single Pill Combinations for Chronic ConditionsWednesday, March 7, 2012
Regular readers will recall the recent FDA advisory committee decision to recommend approval of the single-pill combination of phentermine and topiramate for the treatment of obesity.
In this context, I wish to point out that the use of single-pill combinations (i.e. one pill containing more than one drug), is not a concept unique to obesity. In fact, the use of single-pill combinations for managing chronic diseases like hypertension or diabetes is on the rise.
Much of this trend is explained by the fact that using more than one drug in combination is often more effective than using one drug alone and by matching the right agents, it is possible to use lower doses of the drugs than if they were to be used alone. Sometimes, the ‘side-effects’ of one drug can even reduce or cancel out the ‘side-effects’ of the other, thereby making the combination better tolerated than either drug alone. Finally, putting several drugs into one pill makes it easier for patients, as research shows that patients are far more likely to take one pill than two.
To this point, we now published the results of a trial comparing the blood pressure lowering effect of a single-pill combination of telmisartan and amlodipin (two commonly used antihypertensive agents) to amlodipine alone, in overweight and obese hypertensive patients with type 2 diabetes (Clinical Therapeutics).
Specifically, this 8-week, randomized, parallel-group, double-blind study compare the once-daily single-pill combination of telmisartan 80 mg and amlodipine 10 mg (T/A; n = 352) with once-daily amlodipine 10 mg (A; n = 354) in patients with type 2 diabetes mellitus and stage 1 or 2 hypertension.
Not surprisingly perhaps, the combination resulted in significantly greater decreases in blood pressure levels (-29.0 mm Hg vs -22.9 mm Hg at 8 weeks) with 71% vs 54% of patients achieved the blood pressure goal on the the combination pill. Twenty-four hour ambulatory blood pressure levels were likewise significantly lower in the combination group.
While the fact that combining two drugs lowers blood pressure more than using a single agent alone is not all that astonishing, the combined effects on ‘side-effects’ are perhaps worth mentioning.
Thus, the onset of peripheral edema (a common ‘side-effect’ with the use of calcium channel blockers like amlodipine) was at least numerically less frequent when amlodipine was used in combination with telmisartan.
The issue of ‘side-effects’ cancelling each other out is not new. In the case of the phentermine/topiramate combination, we have seen that the blood-pressure increasing effect of phentermine is ‘reversed’ by the blood pressure lowering effect of topiramate (resulting in a net blood pressure lowering effect of the combination).
Applying such principles, which, as shown in this study, are now increasingly used in other disease areas, to obesity management, may not only allow the use of lower doses but also conveniently mitigate some of the ‘side effects’ that these compounds may have when used alone.
Disclaimer: I have received honoraria and research support from the makers of these agents (Boehringer-Ingelheim and Vivus)
Sharma AM, Bakris G, Neutel JM, Littlejohn TW, Kobe M, Ting N, & Ley L (2012). Single-Pill Combination of Telmisartan/Amlodipine Versus Amlodipine Monotherapy in Diabetic Hypertensive Patients: An 8-Week Randomized, Parallel-Group, Double-Blind Trial. Clinical therapeutics PMID: 22386829