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The discussion will take a practical, problem-oriented approach by following 3 cases:

Case 1

A 53-year-old man was diagnosed with T2DM 6 weeks ago, at which time lifestyle intervention was recommended and treatment with metformin 500 mg twice daily was initiated. The patient began to experience severe diarrhea within a few days of beginning metformin. The diarrhea improved over the next 2 to 3 weeks, but he still experiences 1 or 2 episodes every few days. As a result, he does not want to continue taking metformin.

At diagnosis, the patient’s A1C level was 7.5% and his fasting plasma glucose was 158 mg/dL. He is 6-ft 2-in tall, 236 lb, with a body mass index of 30 kg/m2 and blood pressure of 123/78 mm Hg. The patient works full-time as a building contractor, and he is a current smoker. He has hypertriglyceridemia (266 mg/dL), which is being treated with a fibrate.

Case 2

A 47-year-old man was diagnosed with T2DM 2.5 years ago. His A1C level was 8.8%. He had a good response with lifestyle intervention and metformin 1000 mg twice daily, losing 17 lb over 1.5 years. During that time, his A1C level dropped to 7.2%. Six months ago, treatment with pioglitazone 15 mg was started because his A1C level had risen to 7.8%. His current A1C is 7.0%. He is upset because he has since gained 6 lb, mostly edema, which has raised his blood pressure to 138/87 mm Hg. He refuses to take a diuretic, because hydrochlorothiazide, which was prescribed for essential hypertension, caused him to urinate more often. He wants to discontinue pioglitazone so he will lose weight and regain control of his blood pressure.

The patient is 5-ft 9-in tall, 237 lb, with a body mass index of 35 kg/m2. He works full-time as an office manager. He has essential hypertension, which is being treated with lisinopril and metoprolol.

Case 3

A 68-year-old woman was diagnosed with T2DM 5 years ago. Her A1C value was 8.7%. She was initially managed with lifestyle intervention, but 1 year after diagnosis, treatment with metformin 500 mg twice daily was initiated, and the dose was titrated to 1000 mg twice daily a year later. On this regimen, her A1C level dropped to 7.1%, but 1.5 years later, it had increased to 8.3%. At that time, glyburide 5 mg once daily was added to her treatment regimen and titrated to 10 mg once daily. Mild renal insufficiency (CrClest, 58 mL/min) was identified at today’s visit. Her current A1C is 7.4%.

The patient is 5-ft 3-in tall, 148 lb, with a body mass index of 26 kg/m2 and blood pressure of 122/76 mm Hg. She works part-time as a librarian. She has peripheral arterial disease, which is being treated with aspirin, clopidogrel, and atorvastatin. She also has osteoporosis, which is being treated with ibandronate.

These cases, which represent various stages of disease progression, present important decision points regarding how to initiate or modify therapy. For each of these decision points, many factors must be considered, including underlying pathophysiology, comorbidities, A1C-lowering ability, and previous treatment. Other factors to consider are the safety of available agents, including the risk of hypoglycemia; tolerability; and nonglycemic effects, such as on weight, lipids, and blood pressure.

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