These 3 case studies illustrate the challenges of intensifying treatment in complex T2D patients--and also the options available to individualize that next step.
There is significant flexibility now available when it comes to intensifying pharmacologic treatment for patients with type 2 diabetes (T2D). There is also a growing opportunity to individualize T2D treatment, both when changes to a regimen are needed and at initiation of medical therapy.The following 3 patient case studies illustrate a number of the common comorbidities and complications associated with T2D that make effective management like working on a jigsaw puzzle. With recent FDA label expansions for several classes of T2D drugs, however, it is getting easier to find a perfect fit.Based on your knowledge of the drugs and the science, what is the best next Rx for each of these patients - and why?
Case #1 patient history. A 72-year-old man with T2D and CKD with albuminuria (eGFR 40 mL/min 3 months ago) presents to clinic today. He is having hypoglycemia a few times a week. BG readings, mostly fasting and before dinner, range from 50-200 mg/dL. Metformin has caused him gastric upset in the past.
Answer: C. Stop glimepiride and start canagliflozin 100 mg/d. The sulfonylurea is probably part of the reason for the patient's hypoglycemia, so neither option A or B is appropriate.
Option C (stop glimepiride and start canagliflozin 100 mg/d) is the best answer, given the patient’s frequency of hypoglycemia and CKD. The CREDENCE (Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy) trial showed that in patients with T2D, CKD, & albuminuria, those randomized to canagliflozin had a significantly lower rate of the primary outcome (ESRD, doubling of creatinine, and renal- or CVD-related death) vs placebo.
Canagliflozin also has an FDA indication for risk reduction of ESRD, serum creatinine doubling, and cardiovascular death in patients with type 2 diabetes, nephropathy, and albuminuria.
Case #2 patient history. A 43-year-old woman with T2D, diagnosed at age 37, is in clinic; her A1c today is 8%; she has no micro- or macrovascular complications. She has severe obesity (BMI 42). She is on maximum dose metformin. She is trying to adhere to a healthy diet and also to walk 20 mins/day.
You talk with her about intensifying her antihyperglycemic regimen and she is in agreement, interested in an agent that will help her lose weight.
Answer: B. Oral semaglutide 3 mg/d for 4 weeks, 7 mg/d for 4 weeks, and then 14 mg/d. Glimepiride and other sulfonylureas are associated with weight gain. Sitagliptin and other DPP-4 inhibitors are weight neutral. In the phase 3a PIONEER 2 open-label trial, patients with T2D not controlled on metformin were randomized to either oral semaglutide or empagliflozin. At 52 wks, patients on semaglutide had significantly greater weight loss (P<.02) vs patients on empagliflozin; option B is best.
Case #3 patient history. A 52-year-old man with history of CAD status post CABG and ischemic cardiomyopathy is referred to your clinic by his cardiologist for management of T2D, diagnosed 5 years ago. He has no history of microvascular complications. He takes sitagliptin 100 mg/d & insulin degludec 15 U at night. His A1c today is 8.5%, renal function is normal. He was discharged last month after a hospitalization for volume overload secondary to a HF exacerbation.
Which agent above, if initiated, would benefit the patient in terms of reducing the likelihood of another hospitalization for HF?
Answer: Dapagliflozin 10 mg/d. Only dapagliflozin has an FDA indication to reduce risk of HF hospitalization in patients with T2D. The indication is based on data from the DECLARE-TIMI 58 trial, in which patients with T2D, less than half of whom had established CVD, were randomized to either placebo or dapagliflozin 10 mg/d.