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Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

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 significant...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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 the...
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

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 glucose levels...
Diabetes Mellitus: Type 2 and Gestational01:22

Diabetes Mellitus: Type 2 and Gestational

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...
Diabetes Mellitus: Overview and Type I Subtype01:22

Diabetes Mellitus: Overview and Type I Subtype

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

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 manages...

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Autoimmune Disease Risk With GLP-1RA, DPP-4i, and SGLT2i Treatment in Patients With Diabetes.

Arjun Mahajan1,2, David W Bates1,3, Alessandro Doria1,4,5

  • 1Harvard Medical School, Boston, Massachusetts.

ACR Open Rheumatology
|July 8, 2026
PubMed
Summary

Dipeptidyl peptidase-4 inhibitors (DPP-4i) showed a lower risk for psoriasis and thyroiditis compared to glucagon-like peptide-1 receptor agonists (GLP-1RA). However, DPP-4i increased the risk of dermatomyositis and bullous pemphigoid.

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Electrochemiluminescence Assays for Human Islet Autoantibodies
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Published on: March 23, 2018

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09:15

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Published on: March 23, 2018

Area of Science:

  • Endocrinology
  • Immunology
  • Pharmacology

Background:

  • Dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are common type 2 diabetes treatments.
  • The comparative immunologic safety profiles of these antidiabetic agents remain unclear.

Purpose of the Study:

  • To evaluate the incidence of autoimmune diseases in patients treated with DPP-4i, GLP-1RA, or SGLT2i.
  • To compare the immunologic safety of these widely prescribed medications for type 2 diabetes.

Main Methods:

  • Emulated target trials were conducted using electronic health record data from 152 healthcare organizations (2016-2023).
  • Adults with type 2 diabetes initiating monotherapy with DPP-4i, GLP-1RA, or SGLT2i, without prior autoimmune disease, were included.
  • Propensity score matching balanced cohorts for demographics, comorbidities, and medications, creating large matched pairs for comparative analysis.

Main Results:

  • Dipeptidyl peptidase-4 inhibitors (DPP-4i) were associated with a reduced risk of psoriasis, psoriatic arthritis, and autoimmune thyroiditis compared to glucagon-like peptide-1 receptor agonists (GLP-1RA).
  • Conversely, DPP-4i use was linked to an increased risk of dermatomyositis and bullous pemphigoid relative to GLP-1RA.
  • No significant differences in autoimmune disease incidence were found between GLP-1RA and SGLT2i treatments.

Conclusions:

  • Dipeptidyl peptidase-4 inhibitors (DPP-4i) demonstrate a differential immunologic safety profile compared to glucagon-like peptide-1 receptor agonists (GLP-1RA), increasing risks for certain autoimmune conditions.
  • Findings suggest DPP-4i may reduce psoriasis and thyroiditis risk but elevate risks for dermatomyositis, bullous pemphigoid, and giant cell arteritis compared to GLP-1RA.
  • These results offer crucial safety insights for selecting antidiabetic medications and highlight areas for future research into drug mechanisms and long-term safety.