Practical Strategies for Choosing among Incretin-Based Agents in Type 2 Diabetes, Part 1

Initially, he was started on metformin 500 mg twice daily, a diet with moderate caloric restriction, and an exercise regimen.

After 3 months, metformin was increased to 1000 mg twice daily. His A1c level initially responded and was 6.7% after 1 year of treatment, and 7.1% after 2 years. However, despite his best efforts with lifestyle modification and adherence to metformin therapy, on recent evaluation, Mark's A1c level had risen to 8.4%. To regain glycemic control he was started on glimepiride 2 mg daily in addition to metformin.

His past medical history includes hypertension for which he takes lisinopril 20 mg daily and dyslipidemia for which he takes pravastatin 40 mg daily. Recently, his blood pressure was 130/80 mm Hg and fasting laboratory results indicated a low-density lipoprotein cholesterol (LDL-C) of 150 mg/dL, triglycerides of 160 mg/dL, and high-density lipoprotein cholesterol (HDL-C) of 40 mg/dL. He is a vice president for a marketing firm, travels frequently, and he is concerned about how the side effects of his medications, and their convenience, will fit with his busy work schedule.

Mark now presents 6 months after the addition of glimepiride, having gained 3 kg since that time. His A1c level is 7.6%, and his fasting plasma glucose (FPG) is 142 mg/dL. He reports 3 episodes consistent with hypoglycemia in the past 3 months. One episode, occurring while flying for a business trip, required assistance from another passenger and the flight attendant. Mark is very concerned about his weight gain and the episodes of hypoglycemia.

Which of the following represents the most appropriate A1c treatment target for this patient according to clinical guidelines from the American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD)?

1. Less than 6.5%
2. Less than 8.0%
3. Less than 7.5%
4. Less than 7.0%

Correct answer is 4

The 2009 ADA/EASD guidelines suggest a target A1c level of 15 years who have no or minimal microvascular complications.

T2DM is an increasingly common, complex metabolic disorder, characterized by progressive hyperglycemia and a high risk for both microvascular and macrovascular complications. A substantial body of evidence supports the continuous relationship between the risks for microvascular and macrovascular complications and glycemia, most notably findings from the UKPDS (United Kingdom Prospective Diabetes Study) trial, which is the largest and longest study in T2DM to date. Clinical trial data from UKPDS showed that intensive (median A1c 7.0%) vs conventional (median A1c 7.9%) glucose control significantly lowered the risk for microvascular disease by 25% (P = .0099), although the reduction in cardiovascular events was not significant. An observational analysis of UKPDS data indicated that the risk for any diabetes-related endpoint (diabetes-related death, myocardial infarction, microvascular complications) rose with increasing mean A1c concentration across a wide range of glycemic exposures over time (Figure 1A and 1B); this association was independent of other previously known risk factors and comorbidities including age at diagnosis, ethnic group, systolic blood pressure, lipids, and smoking.^] Specifically, a 1% reduction in A1c levels was associated with a 37% reduction in risk for microvascular complications (P < .0001) and a 21% reduction in the risk for any diabetes-related endpoint, including death (P < .0001).

In addition, each 1% reduction in A1c levels was also associated with a 43% decrease in the risk for amputation or death from peripheral vascular disease (P < .0001). The associations with reductions in glycemia were less steep, though still significant for myocardial infarction (P < .0001), stroke (P = .035), and heart failure (P = .021), as compared with the reductions in glycemia for microvascular complications.