Postprandial Glucose Excursions in Type 2 Diabetes

SOURCE: Yacoub T. Postgrad Med 2017;129:791-800.

One commonly advocated method for approaching correction of hyperglycemia in type 2 diabetes is “fix the fasting first.” Basal insulins have been used commonly to fix fasting glucose, but even with sensible combinations of insulin and oral agents, as many as 40% or more of patients will need to address postprandial glucose excursions (PPG) to attain desirable A1c goals.

In support of maintenance of PPG, epidemiologic data point to an association between PPG and cardiovascular disease risk. Whether management of PPG ameliorates consequences (independently from overall glucose control, especially fasting glucose) has been more difficult to confirm. Repaglinide is a rapid-acting oral agent producing prompt but short-lived insulin secretion from beta cells. Although the receptor site for repaglinide is the same as that for sulfonylureas (e.g., glipizide, glimepiride), it is in a distinct pharmacologic category because it differs structurally from sulfonylureas and lacks a sulfonamide group characteristic of sulfonylureas.

In a clinical trial comparing repaglinide with glyburide, PPG was reduced more with the former; repaglinide also was associated with greater carotid intima media thickness regression. When control of fasting glucose has been achieved but excessive PPG excursions remain, therapeutic choices include adding prandial insulin, alpha-glucosidase inhibitors (e.g., acarbose), or adding glucagon-like peptide-1 receptor agonists (e.g., liraglutide, exenatide). Currently, it is unclear what the preferred method of PPG control should be, but the most recent American Diabetes Association 2018 guidelines suggest that for persons with established cardiovascular disease who have not attained glucose goals, incorporation of agents that have shown cardiovascular risk reduction (i.e., canagliflozin, empagliflozin, liraglutide) should be a priority.

Long-term Outcomes for Obesity

SOURCE: Jakobsen GS, et al. JAMA 2018;319:291-301.

For most patients, managing obesity is a long-term endeavor. Recent proliferation of oral and parenteral anti-obesity agents has increased the number of pharmacologic treatments. Still, long-term weight reduction achieved with such treatments, in combination with lifestyle interventions, is modest (typically, 5-10% body weight decline). Additionally, pharmacologic treatments are not disease-modifying; that is, after medication cessation, weight regain occurs consistently and predictably.

Obesity surgery produces prompt and highly effective metabolic changes that favorably affect prevalent and incident diabetes and hypertension. But do these results last? To answer that question, Jakobsen et al reported on a 10-year follow-up of patients with obesity who were offered their choice of surgical or intensive medical treatment (n = 1,888) at a publicly funded tertiary care obesity center in Norway.

Outcomes differences between the groups were dramatic. Subjects who chose surgical treatment were twice as likely to go into hypertension remission, four times less likely to develop new onset hypertension, and four times more likely to experience remission of diabetes than medically treated subjects. Although surgical intervention was not without adverse effects, including a difficult-to-explain modest increased incidence of depression, metabolic benefits were consistent and enduring. The evidence of the advantages of bariatric surgery over medical management continues to accrue.

Biomarkers for Tight Control of Crohn’s Disease

SOURCE: Colombel JF, et al. Lancet 2018;390:2779-2789.

Colombel et al investigated the effect of including biomarkers, in addition to clinical signs and symptoms, for management of Crohn’s disease. This multinational study enrolled patients with Crohn’s disease into an open-label study with two treatment arms: tight control (i.e., intensification of treatment based on clinical signs and symptoms, as well as optimization based on levels of C-reactive protein and fecal calprotectin) vs. clinical management (treatment intensification based on symptoms/signs of disease activity alone). Main treatments included prednisone, adalimumab, and azathioprine. The primary endpoint was mucosal healing with absence of deep ulcers at 48 weeks.

A statistically significantly greater proportion of subjects in the tight control group achieved the primary endpoint than the clinical management group (46% vs. 30%), while adverse effects and dropouts were similar between the two groups. The authors suggested that treatment escalation based on the combination of clinical symptoms with biomarkers produces more favorable outcomes.