The Basics
First line therapy for diabetes mellitus 2.
What is metformin and Comprehensive Lifestyle Management?
These drug classes have potential benefits for CVD
Atherosclerotic disease: GLP-1 analogues (liraglutide>semaglutide>exenatide extended release) and meformin
Atherosclerotic and CHF: SGLT-2 inhibitors
Mixed bag: TZDs - pioglitazone may benefit atherosclerotic disease but with class risk that may increase CHF exacerbations
This is an oral drug that prevents glucose reabsorption in the renal tubule
What is empagliflozin, dapagliflozin, canagliflozin, erugliflozin?
Metformin
Weight neutral or reduction
65 year old male PMH HTN, obesity, CKD II presents for regular follow up. While reviewing lab work you see that his Hga1c is 7.9 and a urinalysis from his recent ER visit showed 2+ protein. He has taken lisinopril and metformin for many years. What drug should you consider for this patient?
SGLT2 inhibitor (Canagliflozin, dapagliflozin > empagliflozin)
These are considered high risk indicators for DM2
What is age >55 with coronary, carotid or lower extremity artery stenosis >50% or left ventricular hypertrophy?
This drug class can possibly increase the risk of edema and CHF
Thiazolidinediones
This is an oral drug that may cause hypoglycemia in certain populations.
Sulfonylureas: glipizide, glyburide, glimepiride
Increases beta cell insulin secretion
SGLT-2 inhibitors
Weight reduction
Sulfonylureas, typically cost effective ($4 list at Walmart) and dosages can be reduced or use a shorter acting (glipizide) to reduce risk of hypoglycemia in elderly patients
You should consider these comorbid conditions independently of Hga1c target
What is ASCVD, Heart Failure and Chronic Kidney disease?
Give me one good reason (or more) why SGLT2 inhibitors might improve heart failure.
-Promote osmotic diuresis and natriuresis in patients with and without diabetes, and thus may reduce preload
-May also have vascular effects (including improving endothelial function) that promote vasodilation and thus may also reduce afterload
-May improve myocardial metabolism and thus improve cardiac efficiency
-May inhibit the sodium-hydrogen exchanger 1 isoform in the myocardium and thus may reduce cytoplasmic sodium and calcium levels, while increasing mitochondrial calcium levels
-Postulated to reduce cardiac fibrosis and to alter adipokines and cytokine production
-Effects on renal function may contribute to improved outcomes in patients with HF
-Been shown to reduce the risk of atrial arrhythmias by mechanisms that may include reductions in atrial dilation, inflammation, oxidative stress, and sympathetic overdrive
This is likely an injectable drug that may cause GI side effects. Which makes sense because the mechanism mimics secretions from enteroendocrine cells in the gut.
GLP-1 analogues: dulaglutide, exenatide, liraglutide, semaglutide (oral)
Synthetic incretins that stimulate insulin secretion
DPP-4 inhibitors
Weight neutral
75 year old female PMH DMII, HFpEF, HTN, osteoporosis, HLD presents for follow up after recent lab work revealed HgA1c 9.4. She reports that she has been unable to exercise and follow her diet due to caring for her mother following complications of a hip fracture. She's been compliant with metformin and liraglutide for several months but hasn't seen much improvement in HgA1c. What drug class should you avoid in this patient?
SGLT-2 inhibitors - increased risk of fractures
You should consider these agents if minimizing weight gain or promoting weight loss is your goal.
What are GLP1 receptor agonists and SGLT2 inhibitors?
DAILY DOUBLE
True or False: Every diabetic patient should be on a statin.
False: Likely most diabetic patients will need statin therapy but it is individualized based on patient.
Patients aged <40 years: Commence statin treatment based on previous ASCVD event or ASCVD risk >20% in 10 years
Patients aged >40 years: Consider
primary prevention with moderate-dose statin
Triglyceride-lowering agents (e.g., icosapent ethyl) can be considered in
high-risk patients with triglyceride levels ≥150 mg/dL)
A drug from this class should lower your Hga1c but probably not your weight and it may cause you to get pancreatitis
DPP-4 inhibitors: sitagliptin, linagliptin, saxagliptin, alogliptin, vildagliptin
Blocks DPP-4 that causes breakdown of incretins that stimulate insulin secretion
Sulfonylureas and thiazolidnediones
Weight increase
37 year old female PMH obesity, hypothyroidism presents for follow up. Her hypothyroidism has been well controlled for many years and she's recently been trying to improve her health while she's trying to conceive. She had free screening labs through her work and her HgA1c was 6.0. She wants to know if there's any drug that might improve her health or help her lose weight. Do you have any medications to recommend?
Metformin - can decrease weight, prevent transition to DMII, can be continued in pregnancy, may help with PCOS
If you're looking for cheap drugs and a lower Hga1c, these drug classes are for you.
What are sulfonylureas and thiazolidinediones?
DAILY DOUBLE
What are the thresholds for diabetes diagnosis?
Hemoglobin A1c level: >6.5%
Fasting plasma glucose level ≥126
You'll want to start a patient on this drug quickly and then make sure you're gradually titrating the dose up and monitoring for potential B12 deficiency.
What is meformin?
GLP-1 analogues
Weight reduction
70 year old male PMH obesity, HTN, CAD s/p stent x1, bladder cancer in remission, GERD presents for hospital follow up with a partial small bowel obstruction which was complicated by hyperglycemia. HgA1c in the hospital was found to be 12%. He has previously been on several medications including metformin, pioglitazone, glyburide and empaglipflozin but has not recently been compliant with medications. Which medication would you start in this patient?
Basal insulin + empagliflozin/liraglutide