Two Orals Fail in a T2DM Patient

A 63-year-old Hispanic woman who has been under your care for 10 years was diagnosed with type 2 diabetes (T2DM) 6 years ago. In addition to long-standing hypertension and hypercholesterolemia, she has a BMI (body-mass index) of 31 kg/m2 and a family history of cardiovascular disease. However, she has never had a cardiovascular event and does not report any cardiac symptoms. She monitors her fasting glucose level twice a week. Her morning fasting glucose levels have ranged between 140 and 160 mg/dl. She is taking metformin (1,000 mg b.i.d.) and extended-release glipizide (10 mg b.i.d.). You have been seeing her every six months since her diagnosis of T2DM. Her hypertension has been successfully controlled with hydrochlorothiazide (25 mg daily) and lisinopril (20 mg daily) and her hypercholesterolemia with simvastatin (20 mg daily). Additionally, she takes aspirin (81 mg daily).

The patient has struggled to manage her weight and has been counseled about lifestyle changes. Even though she has lost weight on various diets (approximately 10–15 pounds), she regains all of the weight lost. She tries to walk 30 minutes three times a week. Her BMI has fluctuated between 30 and 32 kg/m2 for the past decade.

A recent blood test showed her HbA1c level to be 8.0 percent. Her other laboratory tests have consistently shown normal results for liver, renal, and thyroid function. Physical examination shows normal blood pressure (118/78 mm Hg) and normal cardiorespiratory, abdominal, and neurologic findings.

The patient has health insurance through her employer, which includes prescription drug coverage. Concerned about her inability to reach her glycemic goal (HbA1c of 7.0 percent), she seeks advice about whether a change in medications might help her manage her T2DM more effectively.

Treatment Options

Which one of the following treatment options do you think would be most appropriate for this patient?

The durable glucose lowering and improved insulin sensitivity associated with the TZDs, and their several noteworthy non-glycemic effects, make them attractive options as additions to the treatment regimen of this patient. The wise clinician, however, must also be cognizant of potential adverse effects and contraindications, particularly if this patient, known to be at risk for cardiovascular disease, has any signs of peripheral vascular disease or systemic fluid retention. The clinician should also assess this 63-year-old for fracture risk, because a woman at even moderately high risk of fracture might better be given a different agent.

Compared to insulin glargine or pioglitazone, GLP-1 receptor agonists have similar potential to improve this patient’s glucose levels. These agents are available as easy-to-use pens and, unlike the other options presented, the patient will likely experience satiety and weight loss. In my experience, GLP-1 agonists are very well received by patients. Once the overall glycemic and non-glycemic effects (especially weight loss potential) are described to patients, the need for injection does not present itself as a barrier.

Currently, more than 90 percent of T2DM cases are managed by the primary care community. It should be within the scope of expertise for every primary care provider to recognize the need for and institute basal insulin therapy, when appropriate. When there is failure to maintain goal HbA1C with one or two oral agents, basal analog insulin is a well-studied, effective, and cost-effi- cient way to advance therapy with a minimum of treatment-related sideeffects or safety issues.

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