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Glucagon-like Receptor Agonists01:24

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
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Diabetes: Management and Pharmacotherapy01:15

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The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
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GLP1 Receptor Agonist and SGLT2 Inhibitor Combination: An Effective Approach in Real-world Clinical Practice.

Olaia Díaz-Trastoy1, Rocío Villar-Taibo2, Mildred Sifontes-Dubón3

  • 1Endocrinology and Nutrition Department, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain.

Clinical Therapeutics
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Summary

Combination therapy with sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1RAs) significantly improves glycemic control and promotes weight loss in type 2 diabetes patients. This effective and safe treatment option offers sustained benefits in real-world clinical practice.

Keywords:
GLP1 receptor agonistSGLT-2 inhibitorclinical practicetype 2 diabetes

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Area of Science:

  • Endocrinology
  • Pharmacology
  • Metabolic Diseases

Background:

  • Type 2 diabetes (T2D) management often requires combination therapy for optimal glycemic control.
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1RAs) are effective monotherapies for T2D.
  • Evaluating the synergistic effects and safety of combining SGLT2 inhibitors and GLP1RAs is crucial for clinical practice.

Purpose of the Study:

  • To assess the effectiveness and safety of combined SGLT2 inhibitor and GLP1RA therapy in patients with inadequately controlled type 2 diabetes.
  • To analyze the impact of combination therapy on glycemic control, weight, and renal parameters.
  • To compare the outcomes of simultaneous versus sequential initiation of these drug classes.

Main Methods:

  • Retrospective analysis of electronic prescriptions for patients on SGLT2 inhibitor and GLP1RA combination therapy.
  • Data collection included demographics, HbA1c, glucose, renal function, lipid profile, liver enzymes, uric acid, weight, BMI, blood pressure, and adverse events.
  • Statistical analysis using SPSS, including t-tests, ANOVA, and chi-squared tests to compare outcomes before and after treatment initiation and between different initiation sequences.

Main Results:

  • Combination therapy led to a significant reduction in HbA1c ( -1.1%) and mean weight loss of 3.5 kg.
  • 42% of patients achieved HbA1c <7%, and 40% achieved ≥5% weight loss.
  • Improvements in transaminase levels and renal parameters were observed, with benefits persisting over time. Simultaneous initiation resulted in faster weight loss and greater HbA1c reduction compared to sequential initiation, though long-term metabolic control was similar.
  • Adverse events were rare, and a trend towards reduced insulin dosage was noted.

Conclusions:

  • Combination therapy with SGLT2 inhibitors and GLP1RAs demonstrates significant benefits in glycemic control and weight reduction in a real-world setting.
  • The combined treatment is generally well-tolerated with a low incidence of adverse events.
  • This therapeutic strategy offers a valuable option for managing inadequately controlled type 2 diabetes.