The PHC Blog article on February 6, 2017 gave a very nice overview of the American College of Physicians (ACP) newly released guideline on treatment of Type 2 Diabetes (DM2). I will quickly summarize: start with metformin, then add another medication as needed based upon side effect profile and patient characteristics.
This guideline is very similar to the ADA guidelines. I appreciate the ACP attempt to look at side effects of the different classes of DM2 medications and to avoid certain medications in patients with pre-existing medical conditions. The guideline however doesn’t provide guidance on medication selection based upon cost.. Why does cost effective prescribing matter? Because for every dollar PHC spends on medications, we have to spend less on other health care or enhanced benefits. PHC is a non-profit organization with a 4% overhead. There is not much room for un-necessary spending.
Let’s start first with a simple table of the various choices:
|Class||Example||Action||Cost per month|
|Biguanide||Metformin||Decrease hepatic glucose, increase insulin sensitivity||< $5|
|Sulfonylurea||Glipizide||Increases pancreatic insulin secretion||< $5|
|Meglitinide||Repaglinide||Increases pancreatic insulin secretion||$60|
|Thiazolidinedione||Pioglitazone||Decrease hepatic glucose, increases insulin sensitivity||$10|
|DPP-4||Alogliptin||Increases pancreatic insulin secretion||$430|
|GLP-1 RA||Liraglutide||Increases pancreatic insulin secretion||$550+|
|SGLT-2||Canagliflozin||ncrease urinary glucose secretion||$430|
Metformin is the first choice in all guidelines. Metformin decreases hepatic glucose and increases insulin sensitivity. Start slow (500 mg with the evening meal) – Start slow with 500 mg once daily with the evening meal and, if tolerated, add a second 500 mg dose with breakfast. The dose can be increased slowly (one tablet every one to two weeks) as necessary (per UTD).. The longer acting ER formulation has fewer GI side effects and is on the PHC formulary. Metformin is contraindicated for patients with a GFR < 30. Consider dual therapy at the outset for patients with an A1c > 9% at diagnosis.
If not at target at 3 months with metformin, diet and exercise, add a sulfonylurea (SU) or basal insulin. Repaglinide is an option for patient who don’t reach goal with metformin and cannot take a sulfonylurea and who wish to avoid insulin. It is short acting and may be better for people who skip meals. Pioglitazone is another choice after metformin and a SU, but it should be avoided in patients with a history of heart failure. Generally, a third oral agent will not get a patient to goal however if the A1c is over 8% on metformin and a second oral agent.
Dipeptidyl-peptidase-4 inhibitor drugs, such as alogliptin, work to increase pancreatic insulin secretion and suppress hepatic glucose production. They may decrease an A1c by 0.5 to 1%. A DPP-4 drug may be considered when your patient is close to target, but not yet controlled on metformin and insulin. Alogliptin is a step agent for PHC and is covered if the Rx claims history shows fills for metformin and a second agent (oral or basal insulin).
GLP-1 Receptor Agonists:
Liraglutide is the preferred glucagon-like peptide-1 receptor agonist for PHC. GLP-1 agents increase insulin secretion, suppress hepatic glucose production and slow gastric emptying and thereby increase satiety. They can decrease an A1c by 1 to 1.5%. They may be appropriate agents for patients with a BMI > 30 for patients on metformin and a second oral agent or basal insulin.
Canagliflozin and other sodium-glucose cotransporter 2 inhibitors work by lowering the renal threshold for glucose and increase urinary glucose excretion. The dose has to be adjusted for renal insufficiency. Side effects include UTIs, yeast infections and weight loss. They may also increase LDL cholesterol.
Ultimately, your patient needs what he or she needs after treatment with diet and exercise. The medications will cost what they cost, but it is possible to make cost effective choices that get our patients to goal if we choose with care.
James Cotter, MD MPH; Linette Rey, PharmD