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DPP inhibitors aka -gliptins
All are PO tablets.
Names: Alogliptin, sitagliptin (Januvia), linagliptin (Tradjenta)
Mechanism: Inhibit DPP4 which would otherwise inactivate GLP1. As a result, GLP1 stays activated. GLP1 is an incretin; it reduces gastric motility, stimulates insulin release and decreases glucagon release. After meals, the small intestine normally secretes incretins like GLP1.
Disadvantages: May cause severe joint pain.
CV outcomes: Increased risk of heart failure possible, no augmented risk of HF unlike others in its class (TECOS trial)
GLP1 agonists aka -tides
All are injectable (weekly dosing).
Names: lixisenatide, liraglutide (Victoza), semaglutide (Ozempic), dulaglutide (Trulicity), exenatide (Byetta)
Mechanism: Peptide analogues for GLP1 that agonize GLP1 receptors. GLP1 is an incretin; it reduces gastric motility, stimulates insulin release and decreases glucagon release. After meals, the small intestine normally secretes incretins like GLP1.
Advantages: Liraglutide and semaglutide also used for weight reduction in obese pts.
Disadvantages: Should not be used in patients at risk for pancreatitis.
CV outcomes::
- ELIXA trial: no change in CV risk c/w placebo
- LEADER trial: 13% RR reduction in major CV events in patients at risk
- SUSTAIN-6 trial: 26% RR reduction in CV outcomes with the greatest reduction in nonfatal stroke
SGLT2 inhibitors aka -gliflozins
All are PO tablets.
Names: empagliflozin (Jardiance), canagliflozin (Invokana), dapagliflozin (Forxiga; UK only)
Mechanism: Inhibit distal reabsorption in the nephron of glucose by the Sodium-Glucose Transporter 2 (SGLT2).
Advantages: Secondary effects include reduction in BP independent of diuretic effects and mild weight loss; potentially nephroprotective.
Disadvantages: Use caution in the following at-risk patient groups:
Pts with low BPs need aggressive monitoring particularly during drug initiation; could consider stopping diuretics
Consider reducing insulin and sulfonylureas
Increase in candidal infections possible
May worsen diabetic ketoacidosis when patients are ill and should be withheld on such days-- increase ketone body formation at a low level which contributes to its beneficial effects but when a person is ill this can increase susceptibility to DKA
CV outcomes: EMPA-REG trial showed 14% RR reduction of composite CV outcomes in patients with atherosclerotic disease c/w placebo, no matter the dose of 10-25 per day. 38% RR reduction in CV death, and 35% RR reduction for HF hospitalizations.
PDAPs: Boehringer for legal US residents only; J&J pharmacy card