Clinical Briefs
Liraglutide for Prevention of Diabetes
SOURCE: le Roux CW, et al. Lancet 2017;389:1399-1409.
Prevention of progression from prediabetes (pDM) to type 2 diabetes mellitus (T2DM) is quite a success story. Essentially, each antidiabetic entity that has been trialed (and some weight loss agents) has provided a substantial reduction in the risk of progression from pDM to T2DM. Untreated, clinicians could expect that (in the United States) 6-10% of untreated pDM patients per year will progress to T2DM if no intervention occurs; that number can be reduced by about 25% through several T2DM medications, including metformin, and even more by an intensive program of diet and exercise.
The newest agent to be added to the list of successful agents is liraglutide. In a study of pDM patients (n = 2,254) randomized to liraglutide or placebo and followed for up to three years, incidence of T2DM was 6% in the placebo group vs. 2% in the liraglutide group.
The study subjects in this trial were enrolled multinationally, including countries in Europe, North and South America, Asia, Africa, and Australia. The dose of liraglutide used would be regarded as the “weight-loss dose”; that is, liraglutide under the trade name of Victoza is prescribed for treatment of T2DM up to 1.8 mg/day, but under the trade name of Saxenda is prescribed at 3 mg/day for the treatment of obesity. As would be anticipated, liraglutide treatment produced a significant weight loss: approximately 5 kg greater than the placebo group.
Currently, the most popular pharmacologic treatment for prevention of T2DM in patients with prediabetes is metformin. Several other agents have been shown to produce similar effects, although their use would be off-label.
Surgical Replacement: Younger vs. Older Knees and Hips
SOURCE: Bayliss LE, et al. Lancet 2017;389:1424-1430.
Most patients I have seen who have undergone hip or knee replacement experienced prompt restoration of function and marked reductions in pain. In advanced osteoarthritis sufferers who are as yet untreated surgically, the question often becomes “Should I do it sooner or later?” Waiting until later often entails enduring a significant symptom burden as well as limited mobility; doing it sooner may feel premature to patients with moderately disabling symptoms.
Bayliss et al provided substantiation for “doing it later” (i.e., later by one’s chronologic clock). They assessed data on more than 63,000 individuals who had undergone hip or knee replacement. Hip and knee replacements were shown to be very durable, in that more than 95% of hip or knee replacements were functioning 10 years later, and more than 85% were functioning 20 years later.
However, when specifically looking at the relationship between age at intervention and need for revision, they found that study subjects > 70 years of age who underwent joint replacement surgery experienced a seven-fold lower incidence of revision than patients ≤ 50 years of age (5% lifetime revision rate for the former vs. 35% for the latter). Although the joint replacement decision always should be individualized, these data suggest that we inform potential subjects of the greater likelihood for repeat surgery if initial surgery is performed on patients < 70 years of age.
Spinal Manipulation for Low Back Pain
SOURCE: Paige NM, et al. JAMA 2017;317:1451-1460.
Several interventions for low back pain (LBP) have been demonstrated to improve time to resolution modestly, but no particular treatment has been identified that provides a strong therapeutic advantage over another consistently. Analgesics, anti-inflammatory agents, muscle relaxants, exercise, physical therapy, and spinal manipulation therapy (SMT) each have supportive evidence for efficacy, but SMT has been the object of contentious arguments.
Paige et al reviewed the efficacy and safety of SMT by including 15 randomized, controlled trials (n = 1,711). They concluded that SMT provides a modest statistically significant improvement in pain: approximately 10 points on a 100-point visual analogue scale. They described the harms of SMT as generally transient and minor. Whether the degree of pain reduction attributed to SMT reported here will satisfy many clinicians is questionable. Previous evidence has indicated that at least a 30% reduction in pain from baseline is what patients recognize as clinically meaningful, and these data only indicate a 10% pain reduction. Additionally, the serious adverse effects that have been noted about high-velocity manual medicine techniques (e.g., arterial dissections and paralysis after cervical spine manipulation) occur with insufficient frequency to be reliably detected within such a limited data set.
In this section: drug therapy for diabetes; timing surgical knee and hip replacement; and treating low back pain.
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