Glucagon Like Peptide-1 Receptor Agonist (GLP1-RA) Drug Therapy Update
COMING SOON: AN ORAL GLP1RA is under FDA Review!!
The current ADA Standards of Care algorithm prioritizes patient centered care and shared decision making based on patient preference and presence of comorbid cardiovascular or renal conditions, access, cost and insurance coverage. In addition to lifestyle modification and metformin (1stline), GLP1-RAs and sodium glucose co-transporter 2 inhibitors (SGLT2I) drugs are PREFERRED in patients with:
- Established ASCVD (specific agents based on CV Outcome Trials(CVOTs)
- GLP1RAswith proven benefit: liraglutide, semaglutide, dulaglutide
- SGLT2I with proven benefit: empagliflozin, canagliflozin
- CKD or Heart Failure
- SGLT2I is preferred unless eGFR < 45 ml/min (empa-, cana-, dapaglflozin)
- GLP1RA preferred when eGFR is < 45 ml/min (lira > sema> dula> exenatide ER)
- Weight loss is a priority
- Low risk of hypoglycemia is a priority
The GLP1RA agents have many advantages: they replace insufficient GLP1 production in patients with type 2 diabetes and act as a direct agonist on incretin receptors to correct the underlying pathophysiology in the pancreas, liver, intestines, and brain. They induce glucose-dependent insulin secretion, slow gastric emptying time, and improve satiety, which all leads to improved blood glucose levels, weight loss, and potential improvement of beta cell function. (see chart at the end of the article for the Pros/Cons of GLP1RAs).
The main limitation is that they are INJECTABLE. However, the first ORAL GLP1RA, Semaglutide, was submitted to the FDA for a Priority New Drug Review on March 21, 2019. Priority review can mean approval within the next 6 months.
The information so far:
- Semaglutide 3mg, 7mg and 14 mg once daily oral tablet
- Indication:For the treatment of Type 2 diabetes AND for CV risk reduction in adults with T2DM.
- Trial Data: The summary of the 10 PIONEER trials showed:
- Overall A1C reduction 0.5 – 1.5%
- superiority to empagliflozin and sitagliptin, non-inferiority to liraglutide
- Weight loss: 3 – 11 lb (closest competitor empagliflozin)
- ADRs: Nausea rate 5 – 20%
- CVOT
- 51% reduction in CV death (HR 0.49)
- Non-significant reduction in non-fatal MI (HR 1.18) or non-fatal stroke (HR 0.74)
- 49% reduction in all-cause mortality (HR 0.51)
- Administration:
- Bioavailability is low (< 0.01%). For protection from degradation, the drug with use a SNAC-mediated absorption enhancement to give local pH protection to the drug for transcellular absorption in the stomach.
- For best results, patient will need to take first thing in the morning with 4 ounces of water, then wait 30 mins before eating/drinking/taking other medications.
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