Pharmacology Case Discussion #2- Prof. County Online Clinical Rotation

M.M., a 63-year-old woman, has had Type 2 diabetes for 10 years. She is currently taking Metformin 500 mg PO TID & insulin glargine 47 units at bedtime.
Her A1C is 8.2%. She tries to follow a meal plan that a dietitian developed for her but her BMI remains 31 kg/m². Her physical activity is limited because of an arthritic knee, for which she plans to have knee replacement surgery in the future. Other medical problems include HTN, and dyslipidemia, which are both well controlled. Her medications are HCTZ 25 mg PO Daily, benazepril 40 mg PO Daily, and atorvastatin 40 mg PO Daily. M.M’s niece, who accompanied her for todays office visit, subtly hinted that she has recently began trying to monitor M.M’s memory.

1. Can any antidiabetic agent/s be added to M.M’s current therapy?
2. Please list complete regimen(name, dose, route, frequency) of any added agent/s
3. Please state rationale for choice of any agent/s added

Ms. M.M. has an A1C of 8.2% while being on dual therapy Metformin (biguanide) 500 mg PO TID and insulin glargine (long acting insulin/basal insulin) 47 units at bedtime. Her ideal target A1C is ≤7.0 % thus in order to achieve this goal she should be placed on triple therapy by adding a Thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor or GLP-1 receptor agonist.

Things to consider when choosing the appropriate add on therapy is the efficacy of lowering A1C, if there are hypoglycemic risks, the patients weight and weight concerns, side effects, and costs. As per UpToDate patients who fail to achieve their targeted A1C with a combination treatment, they suggest starting a GLP-1 receptor agonist. This is because GLP-1 receptor agonists have a high efficacy of lowering ones A1C, are associated with a lower hypoglycemia risk, and may promote weight loss.

A GLP-1 receptor agonist may affect glucose control through numerous mechanisms such as boosting of glucose-dependent insulin release from pancreatic islet cells, delaying gastric emptying, and reducing postprandial glucagon and food intake. GLP-1 receptor agonists come in short and long acting, and for Ms. M.M since we do not know if she has any history of ASCVD preference is given to long acting agents due to convenience, but preference and payer coverage can also be considered.

Also the data from directly compared GLP-1 receptor agonists does not show preference of one drug over another. Furthermore there are no comparative trials on the effects of different GLP-1 receptor agonists on long-term outcomes such as complications, health-related quality of life, or mortality. For Ms. M.M I would prescribe Liraglutide once daily injectable. In some studies Liraglutide has shown significantly greater reduction in weight compared to exenatide, albiglutide, and dulaglutide. Likewise Liraglutide has led to greater reduction in A1C than other GLP-1 receptor agonists. Moreover since there are concerns for Ms. M.M’s memory I choose a once daily injection so if she forgets one dose she would still be able to continue it next day as long as there interruption for >3 days. A weekly injection can also be considered but I was afraid if she had forgot one dose she might not obtain her dose until one week later.

Liraglutide is available in prefilled pens and the initial does is 0.6 mg once daily for the first week to reduce GI side effects. Then the dose is increased to 1.2 mg once daily for one week. It can be increased to max 1.8 mg/day if blood glucose goal is not reached.

Additionally since her niece brought up concerns about Ms. M.M’s memory I would want to ensure that the patient is properly taking her medications in regards to the dosing, timing, route, and drug itself. Also for patients with diabetes lifestyle changes should be addressed especially since the patient is obese with a BMI of 31 kg/m². So I would also inquire about patients diet and meal plan along with her physical activity/exercise to help her lose weight.

Medication Profile

• Metformin 500 mg PO TID
• Insulin glargine 47 units at bedtime
• HCTZ 25 mg PO Daily
• Benazepril 40 mg PO Daily
• Atorvastatin 40 mg PO Daily
• Liraglutide 1.2 – 1.8 mg SC Daily

Resources:

1. https://www.uptodate.com/contents/management-of-persistent-hyperglycemia-in-type-2-diabetes-mellitus
2. https://www.uptodate.com/contents/glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064617/