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Management of Outpatients With Diabetes at High Risk of Hypoglycemia

Author/s: 
Celeste C Thomas, Karishma Chopra, Andrew M Davis

More than 30 million people in the US have diabetes, approximately 5% with type 1 and approximately 95% with type 2. About 5 million individuals in the US with type 2 diabetes use insulin and 7 million take sulfonylureas; both of these medications have a greater association with hypoglycemia than metformin, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium-glucose cotransporter 2 inhibitors. Each month, 70% of people with type 1 diabetes experience some degree of hypoglycemia.1 Level 1 hypoglycemia is defined as blood glucose of 54 to 70 mg/dL; level 2 is less than 54 mg/dL; and severe hypoglycemia (level 3) occurs when low blood glucose levels cause neurologic or physical symptoms that require help from others. Furthermore, recurrent severe hypoglycemia increases risk of future dementia.2 Hypoglycemia occurs more often in people with lower education, lower income, and food insecurity.3 This synopsis focuses on outpatient management of diabetes with high risk of hypoglycemia; the guideline also addresses prevention of hypoglycemia in hospitalized patients.4

Keywords 
diabetes Diabetes and Endocrinology Endocrinology insulin

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

Author/s: 
Zheng, Sean L., Roddick, Alistair J., Aghar-Jaffar, Rochan, Shun-Shin, Matthew J., Francis, Darrel, Oliver, Nick, Meeran, Karim

IMPORTANCE:

The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown.

OBJECTIVE:

To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis.

DATA SOURCES:

MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017.

STUDY SELECTION:

Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment.

DATA EXTRACTION AND SYNTHESIS:

Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed.

MAIN OUTCOMES AND MEASURES:

The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia.

RESULTS:

This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]).

CONCLUSIONS AND RELEVANCE:

In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

Keywords 
SGLT-2 inhibitors GLP-1 agonists hypertension
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