Related Experiment Video
Updated: Jan 12, 2026
08:18
A Model of Chronic Nutrient Infusion in the Rat
Published on: August 14, 2013
13.1K
Risk-Benefit Trade-offs of GLP-1RAs and SGLT-2is in Type 2 Diabetes Mellitus (T2D): Systematic Review, Meta-Analysis,
Samit Ghosal1, Anuradha Ghosal2
1Nightingale Hospital, 11 Shakespeare Sarani, Kolkata, West Bengal, 700071, India. ramdasghosal@gmail.com.
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) offer cardiorenal benefits for type 2 diabetes mellitus (T2DM). SGLT-2is excel in reducing heart failure hospitalizations and renal events, while GLP-1RAs show a net benefit for major adverse cardiovascular events.
Area of Science:
- Cardiology
- Endocrinology
- Nephrology
Background:
- Established cardiorenal benefits of GLP-1RAs and SGLT-2is in T2DM.
- Previous meta-analyses lacked cross-class comparisons and net benefit analyses with updated CVOTs.
Purpose of the Study:
- To systematically review and meta-analyze updated cardiovascular outcome trials (CVOTs).
- To compare GLP-1RAs and SGLT-2is regarding cardiorenal benefits and safety.
- To conduct net benefit analyses integrating updated CVOT data.
Main Methods:
- Systematic review and meta-analysis of 17 CVOTs (N=132,038).
- Synthesis of MACE, hHF, renal composites, and safety outcomes using random-effects models.
- Innovative graphical syntheses and net benefit calculations (ARRs minus AERs).
- Risk of bias (RoB 2) and GRADE certainty assessment.
Main Results:
- Both drug classes reduced MACE (HR 0.87).
- SGLT-2is were superior for hHF (HR 0.69) and renal outcomes (HR 0.68).
- GLP-1RAs increased retinopathy (RR 1.18); SGLT-2is increased genitourinary infections (RR 3.34) and DKA (RR 2.67).
- Net benefits favored GLP-1RAs for MACE and SGLT-2is for hHF and renal outcomes under specific assumptions.
Conclusions:
- Innovative integration of updated CVOTs, cross-class comparisons, and risk-benefit tools refines therapeutic decision-making.
- Highlights tailored T2DM management based on patient-specific cardiorenal risks.
- Supports individualized treatment strategies for type 2 diabetes mellitus.
Related Concept Videos
01:24Glucagon-like Receptor Agonists
828
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.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
828
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
568
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...
568
01:23Dipeptidyl Peptidase 4 Inhibitors
570
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...
570
01:22Diabetes Mellitus: Type 2 and Gestational
4.3K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
4.3K
01:06Oral Hypoglycemic Agents: Glinides
577
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...
577
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
511
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.
Acarbose and miglitol are...
Acarbose and miglitol are...
511