Hypertension and Glucotoxicity in a Patient With Newly Diagnosed Type 2 Diabetes: Treatment Recommendations

Mr Smith has newly diagnosed type 2 diabetes mellitus. His HbA1c is 9.1; his BMI is 35; triglycerides, 220; HDL 37; blood pressure, 150/94 mm Hg. His renal function is normal.

I would treat Mr Smith’s elevated blood pressure with an ACE inhibitor. Hypertension is very common in people with diabetes; in this patient’s case, it may have been present for 5 to 10 years before the hyperglycemia appeared.

I would not use any medication for his elevated triglycerides and low HDL at this time. Both may return to normal with lifestyle changes and treatment of the hyperglycemia. His hyperglycemia will most likely require 2 medications unless insulin is used.
One option is short-term insulin to eliminate the glucotoxicity. I would avoid long-term insulin therapy at this point-especially given the patient’s elevated BMI and the weight gain associated with insulin.

Two medications will be needed to obtain a significant reduction in HbA1c in this patient. One medication will only provide a up to 1% reduction in HbA1c. Metformin is the natural first drug choice, but the second drug choice is not as clear. A sulfonylurea or pioglitazone would add an additional 1% reduction, but both are associated with weight gain.

A DPP-4 inhibitor will only reduce the HbA1c an additional 0.5%; however, these agents are not associated with weight gain. I would choose a GLP-1 agonist (exenatide, liraglutide). These agents will provide a 1% or more reduction in HbA1c and will produce a 4 to 8 pound weight loss, thus increasing the chances of reducing the HbA1c to less than 7. GLP-1 agonists also reduce blood pressure and lipid abnormalities, independent of weight loss._¹

Because diabetes was newly diagnosed in this patient, I would attempt to reach an HbA1c goal as close to 6% as possible. The UKPDS study of newly diagnosed diabetes revealed a legacy effect for early aggressive treatment.² That study showed that there was less CV disease in those patients who were treated aggressively early in the disease. Some animal studies also indicate that early aggressive treatment may preserve the pancreatic beta cell.

Note that the ACCORD study suggests that aggressive treatment may be harmful. However, that study was performed in patients with long-term diabetes-some of whom had significant comorbidities.³ An ACCORD substudy of patients who had diabetes for less than 8 years and who had no comorbidities indicated a reduction in CV events for those treated aggressively.

References
1. Garber A, Henry R, Ratner R, et al. LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373:473-481. http://www.ncbi.nlm.nih.gov/pubmed/18819705.
2. Holman RR, Paul SK, Bethel MA, et al. 10-Year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1-13. http://www.ncbi.nlm.nih.gov/pubmed/18784090.
3. Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559. http://www.ncbi.nlm.nih.gov/pubmed/18539917.