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Non-insulin Diabetes Mellitus Medications with Case

by Michael Lazarus

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    00:00 In this case, a 57-year-old man presents to his primary care physician for follow-up of his diabetes. He has been diagnosed with type 2 diabetes 3 months ago and has been started on metformin and lifestyle modifications. The patient does not have any current complaints except for occasional numbness in both hands and feet. His hemoglobin A1c is 8.5% and his serum glucose is 240 mg/dL.

    00:27 What is the best next step for managing this patient? The best next step is to obviously add a second agent to treat his diabetes. Once lifestyle modifications have been initiated and metformin has been started and dose maximized, if the patient continues to have elevations of hemoglobin A1c and serum glucose, a second oral agent is usually indicated. Second line therapy for type 2 diabetes after dosing metformin. After initiating metformin, if the hemoglobin A1c remains above goal, the best next step is to add a basal insulin or a non-insulin agent. This table overviews most of the non-insulin diabetes medications that are important. Starting with the sulfonylureas, an example being glipizide. Adverse effects with these agents are weight gain and hypoglycemia as well as rashes. Effect on weight is to increase the weight and should be used with caution in patients whose renal clearance is decreased as in kidney failure. This will prolong the action of the medication and result in hypoglycemia. Metformin is listed here. The adverse effects that one encounters include diarrhea and abdominal pain. Also note that lactic acidosis is an unusual but worrisome side effect of metformin and usually is increased in the setting of those patients who are going for intravenous contrast testing. So please be aware of this and recommend that the patient stop taking the metformin before their radiologic procedure. Effect on weight of metformin is usually to decrease it but taking and aggravating it is usually neutral. Caution in use of metformin should also be exercised in patients with renal dysfunction. But as you can see here, the glomerular filtration rate has to be fairly low less than 30 mg/min in order for the metformin dose to be decreased. In fact, there is evidence now that dosing patients with moderate or mild renal insufficiency with metformin improves their overall outcomes. The alpha glucosidase inhibitors include agents like acarbose. These are medications that promote carbohydrate excretion from the gastrointestinal tract. Unfortunately, owing to its mechanism of action, adverse effects include abdominal discomfort. Effect on weight is neutral and this medication should also be avoided with kidney dysfunction. The thiazolidinediones, examples of which include the glitazone family of medications can cause weight gain, they can cause heart failure. They have been associated with macular edema and bone problems as well as bladder cancer. They also increase weight and caution should be exercised in patients who have cardiovascular disease because of a higher documented mortality in the case of rosiglitazone, one of the medications within this class of drug.

    03:30 The mitiglinides, which include repaglinide, also has the adverse effect of weight gain and low glucose and should be moderated in patients whose kidney is not functioning normally. The amylinomimetic class of agents have adverse effects of nausea and vomiting but they do have a positive effect on weight. They should also be used with caution in patients who have hypoglycemia especially in conjunction with insulin. The glucagon-like peptide mimetics like Exenatide also have nausea and vomiting as adverse effects but positive effects on weight. Unfortunately, there is an increased risk of pancreatitis and kidney failure with this class of drug. The dipeptidyl peptidase inhibitors like sitagliptin also cause nausea, rash, and can lead to the high incidence of infections. They have a neutral effect on weight and unfortunately because of their mechanism of action can cause pancreatitis and heart failure. And then finally, the sodium glucose transporters such as the gliflozin family of drugs. They increase the incidence of fungal infections and can cause urinary tract infections but have a positive effect on weight. The caution should be exercise with using these drugs because of increased hypoglycemia risk when used in conjunction with insulin.

    05:00 Also use caution when patients have a history of peripheral vascular disease. Choosing agents for diabetes management. The general principles here revolve around the patient's weight. As you can see from the evaluation of all of the medications, all the different agents have variable effects on patient's weight control ranging from increasing weight to decreasing weight to neutral effects.

    05:25 The weight-neutral drug classes include the alpha glycosidase inhibitors like acarbose and the dipeptidyl peptidase 4 inhibitors. If weight loss is the desired effect, consider glucagon-like peptide 1 or the GLP-1 mimetics like pramlintide or sodium glucose transporter 2 inhibitors like the exenatide family of drugs. Weight gain is likely with the use of insulin, sulfonylureas, thiazolidinediones, and mitiglinides.


    About the Lecture

    The lecture Non-insulin Diabetes Mellitus Medications with Case by Michael Lazarus is from the course Diabetes Mellitus. It contains the following chapters:

    • Case 57-year-old Man with Type 2 DM and Numbness
    • Non-Insulin DM Medications

    Included Quiz Questions

    1. Addition of a second oral hypoglycemic agent
    2. Bariatric surgery
    3. Switching to a subcutaneous insulin pump
    4. Increasing the dosage of metformin
    1. Lifestyle modifications → oral metformin → GLP-1 agonist → insulin
    2. Lifestyle modifications → SGLT2 antagonist -> oral metformin -> insulin
    3. Lifestyle modifications → insulin → oral metformin → second oral agent
    4. Lifestyle modifications → insulin → oral metformin → second injectable agent
    5. Lifestyle modifications → empagliflozin → oral metformin → insulin
    1. 54-year-old man with CKD V
    2. 36-year-old woman who had chest CT with contrast last week
    3. 79-year-old man with an HbA1c level of 7.6% who is receiving insulin therapy alone
    4. 45-year-old woman with an eGFR of 27
    5. 15-year-old boy with newly diagnosed type 1 diabetes
    1. Insulin and weight gain
    2. Metformin and weight gain
    3. Sulfonylureas and hyperglycemia
    4. Thiazolidinediones with cardiovascular protection
    5. GLP-1 agonist with increased risk of UTI

    Author of lecture Non-insulin Diabetes Mellitus Medications with Case

     Michael Lazarus

    Michael Lazarus


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