ORAL SEMAGLUTIDE

https://meditropics.com/oral-semaglutide/

*Paridhi Singhal

*Post-graduate Resident, Lady Hardinge Medical College

 

INTRODUCTION:

GLP-1 receptor agonists increase insulin secretion, decrease glucagon and decreases rate of gastric emptying, promoting appetite loss and modest amount of weight loss. Short acting GLP-1 receptor agonists are – exenatide, liraglutide and lixisenatide, these are mostly used to control post prandial glucose.Long acting GLP-1 receptor agonists are- sustained release exenatide, dulaglutide, lixisenatide and semaglutide, which are administered weekly and target both fasting and post prandial glucose levels[1].

Recently, orally administered semaglutideis has been approved, that shows gastric absorption, avoiding proteolytic degradation in small intestine. All these agents are resistant to dipeptidyl peptidase IV mediated enzymatic inactivation.

Liraglutide and semaglutide are used in obesity, have cardiovascular benefits and protective against diabetic kidney disease.

 

MECHANISM OF ACTION:

GLP-1 stimulates glucose dependent insulin secretion from pancreatic beta cells, suppresses glucagon secretion from pancreatic alpha cells and delays gastric emptying. SNAC (sodium N-(8-[2-hydroxylbenzoyl]amino)caprylate), is attached to the oral formulation of semaglutide, that enhances its absorption in the stomach by increasing the local pH and increases drug solubility. It protects against proteolytic degradation [2].

 

PHARMACOKINETICS:

Absorption – time to peak – 15-35 min

Bioavailability- 0.8%[3]

Food interferes with semaglutide absorption.

Atleast 30 min post semaglutide, fasting is recommended.

T1/2 is 1 week

 

Drug- drug interaction: It interacts with levothyroxine by increasing its exposure by 33%. Thus, thyroid function test monitoring is required [3]. No other drug interactions are seen.

INDICATION:

  • Obesity
  • Weight management in diabetic patients
  • Diabetic patients with high ASCVD risk
  • Diabetic patients with CKD, when SGLT-2 inhibitors are contraindicated, or not effective.
  • Diabetic patients with high HbA1c lowering target, in combination with insulin[4].

DOSING:

  • Recommended starting dose is 3mg/day
  • Target maintenance dose: 7mg/day for at least 4 weeks

                                                                

DOSAGE MODIFICATIONS: No modification is required for hepatic or renal impairment.

ADVERSE DRUG REACTIONS: Nausea, Vomiting, Diarrhea, Diabetic retinopathy, Acute pancreatitis, Hypoglycemia, Tachycardia, Acute kidney injury, Gall bladder related illness, Hypotension

 

CONTRAINDICATIONS:

  • Medullary carcinoma of thyroid
  • Multiple endocrine syndrome
  • Acute pancreatitis

CAUTIONS:

  • It is seen to increase risk of thyroid C-cell tumors in rodents and are contraindicated in individuals with medullary carcinoma of the thyroid or multiple endocrine neoplasia.
  • It is reasonable to avoid semaglutide in patients with pancreatic disease or with other significant risk factors for acute pancreatitis (e.g., heavy alcohol use, severely elevated serum triglycerides, hypercalcemia)[5].

REFERENCES:

  1. Powers AC, Fowler MJ, Rickels MR”Diabetes Mellitus: Management and Therapeutics.” Chapter 404 Harrison’s Principles of Internal Medicine, 21e Eds. New York: Joseph Loscalzo, et al. McGraw Hill, 2022, p.3104-3120
  2. Hughes S, Neumiller JJ. Oral Semaglutide. Clin Diabetes. 2020;38(1):109-111.
  3. Overgaard RV, Navarria A, Ingwersen SH, Bækdal TA, Kildemoes RJ. Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials. Clin Pharmacokinet. 2021;60(10):1335-1348.
  4. American Diabetes Association; Standards of Medical Care in Diabetes—2022Abridged for Primary Care Providers. Clin Diabetes 1 January 2022; 40 (1): 10–38
  5. Smits MM, Van Raalte DH. Safety of Semaglutide [published correction appears in Front Endocrinol (Lausanne). 2021 Nov 10;12:786732]. Front Endocrinol (Lausanne). 2021;12:645563.