Costs of Drugs for Treatment of Type 2 Diabetes Mellitus

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.

Next Steps:

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.

DPP-4 Inhibitors:

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.

SGLT-2 Inhibitors:

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



Your patient is hospitalized and in critical condition, unable to make self-determinations for care, to whom do you turn, whose direction do you follow? This situation is problematic when there is no advanced directive or POLST available and the clinical team concludes a particular intervention or set of interventions would constitute futile care.. What are your options as the treating doctor? In the situation where the treating clinical team is interacting with the named or default patient surrogate, there exists the real possibility that conflict will arise. One source of insight on addressing this conflict comes from the ethicists working with the AMA summarized in the linked article.

The above scenario is a common issue, particularly in the ICU. Medical technology has advanced to the point to where it is virtually possible to keep an individual alive (or at least their organ systems functioning) through mechanical and/or chemical intervention almost indefinitely. At some point depending on the medical team and hospitals willingness to persist,  the recommendation not to pursue futile care is made to the surrogate. If the surrogate disagrees, the options open to the treating team seem to be obtaining additional counsel in the form of a palliative care team or ethics consultation AND/OR transfer the patient to the care of another team who is more aligned with the surrogates.

In the scenario where the treating team has run out of transfer options, the ethics committee agrees and recommends not pursuing futile care, and yet the surrogate persists in their directive. Does the treating team have the option of designating an alternative surrogate more closely aligned with their recommendation. The AMA code of ethics provides some guidance on answering this question.

“Though the surrogate’s decision for the incompetent patient should almost always be accepted by the physician, there are four situations that may require either institutional or judicial review and/or intervention in the decision-making process: (1) there is no available family member willing to be the patient’s surrogate decision-maker; (2) there is a dispute among family members and there is no decision maker designated in an advance directive; (3) a health care provider believes that the family’s decision is clearly not what the patient would have decided if competent; and (4) a health care provider believes that the decision is not a decision that could reasonably be judged to be in the patient’s best interests. When there are disputes among family members or between family and health care providers, the use of ethics committees specifically designed to facilitate sound decision making is recommended before resorting to the courts.”

This code indicates that a) surrogates directions are usually required to be adhered to, and b) can be disputed by the physician and ethics consultation and/or legal intervention to change surrogate IF the treating team believes the surrogate is not acting in the patients best interests. This implies some freedom but also a process if the treating team believes what the surrogate is directing is not in the best interest of the patient or represents substituted judgement. A case example might be a transgender individual whose default surrogate was a parent who had been distanced by the patient. In this case, could the patient’s partner be appointed surrogate by the physician. The answer is maybe. However, this would need to follow a process that might include ethics or palliative care consultation, facilitated ‘family’ meetings, and reference to the court to appoint the surrogate. It is important to be aware that the outcome of this process may led to the outcome desired by the clinical team, or may result in recommendation to adhere to the surrogate’s wishes.