ABSTRACT
AIMS: The risk of cardiovascular disease is often underestimated in women. This leads to a delay in controlling the risk factors for cardiovascular disease and even delays in prescribing medications with cardiovascular benefit. Our aim was to explore if glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter-2 inhibitor (SGLT-2i) medications would reduce cardiovascular events in women with type 2 diabetes when atherosclerotic cardiovascular disease (ASCVD) predominates. MATERIALS AND METHODS: We searched for randomized trials comparing GLP-1RA or SGLT-2i to placebo in people with type 2 diabetes and had a primary outcome exploring major adverse cardiovascular events (MACE). Data concerning women were then extracted. A sensitivity and subgroup analyses were performed according to the class of diabetes medication. RESULTS: A total of 9 trials (GLP-1RA in 6 trials and SGLT-2i in 3) were included. Of the 84,258 participants enrolled, 30,784 (37%) participants were women. Pooled results showed a statistically significant lower incidence of MACE favouring diabetes medications (GLP-1RA or SGLT-2i) compared to placebo (RR [95%CI]=0.87 [0.80, 0.94]). On restricting the analysis to GLP-1RA then to SGLT-2i, results remained significant with GLP-1RA but not SGLT-2i. CONCLUSIONS: In women with type 2 diabetes who either have increased cardiovascular risk or established cardiovascular disease and ASCVD predominates, GLP-1RA significantly reduce the incidence of MACE while SGLT-2i result in a non-significant reduction. SGLT-2i may have comparable effect when examined in more studies. GLP-1RA and SGLT-2i should be considered without delay in women with type 2 diabetes and increased risk for cardiovascular disease.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor , Sodium-Glucose Transporter 2 Inhibitors , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/complications , Female , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/therapeutic use , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
AIMS: Our aim was to compare once-weekly semaglutide to incretin-based therapies - defined as either dipeptidyl peptidase-4 inhibitors (DPP-4i) or other glucagon-like peptide-1 receptor agonist (GLP-1RA) - in patients with type 2 diabetes. METHODS: We searched for randomized trials comparing once-weekly semaglutide to other incretin-based therapies in patients with type 2 diabetes. We pooled trials that compared semaglutide to other GLP-1RA together, and those comparing semaglutide to DPP-4i together. The primary outcome was the change in haemoglobin A1c over time. RESULTS: Five trials met our inclusion criteria. There was a significantly greater reduction in haemoglobin A1c favouring semaglutide when compared to other GLP-1RA or DPP-4i [MD (95% CI) = -0.38% (-0.62, -0.15) and -1.14% (-1.53, -0.75) respectively]. There was a significantly greater weight loss favouring semaglutide when compared to other GLP-1RA or DPP-4i [MD (95% CI) = -2.50 kg (-3.91, -1.09) and -3.19 kg (-3.66, -2.72) respectively]. The proportion of patients achieving glycaemic goals and goal weight loss was greater in semaglutide-treated patients when compared to either other GLP-1RA or DPP-4i. However, semaglutide-treated patients had a significantly higher incidence of gastrointestinal side effects. CONCLUSIONS: While both once-weekly semaglutide and other incretin-based therapies can reduce haemoglobin A1c, semaglutide causes a more potent haemoglobin A1c reduction and greater weight loss when compared to other incretin-based therapies. However, this potent effect of semaglutide was associated with a higher incidence of gastrointestinal side effects. Additional studies are needed to determine whether this marked reduction in both haemoglobin A1c and body weight may translate into improved cardiovascular outcomes.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptides/administration & dosage , Hypoglycemic Agents/administration & dosage , Incretins/administration & dosage , Adult , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Drug Administration Schedule , Drug Therapy, Combination/adverse effects , Female , Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors , Glucagon-Like Peptides/adverse effects , Glycated Hemoglobin/analysis , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/adverse effects , Incretins/adverse effects , Male , Middle Aged , Randomized Controlled Trials as Topic/methods , Randomized Controlled Trials as Topic/statistics & numerical data , Treatment OutcomeABSTRACT
AIMS: Our aim was to compare Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) to Dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to metformin. METHODS: We searched for randomized trials comparing SGLT-2i to DPP-4i as add-on therapy to metformin in Type 2 diabetes.We pooled trials reporting outcomes between 12 and 26 weeks together while trials reporting results ≥52 weeks were pooled together. The primary outcomes were the change in haemoglobin A1c (A1c) at ≤26 and ≥52 weeks. Sensitivity analyses were performed according to the dose of SGLT-2i and according to baseline A1c for the primary outcomes. RESULTS: Seven trials met our inclusion criteria. There was a statistically significant reduction in A1c at ≥52 weeks favouring SGLT-2i compared to DPP-4i (MD [95% CI]=-0.11% [-0.20, -0.03]) but no significant difference at ≤26 weeks (MD [95% CI]=-0.05% [-0.16, 0.05]). SGLT-2i caused significantly more weight loss compared to DPP-4i at ≤26 weeks and ≥52 weeks (MD [95% CI]=-2.31kg [-2.66, -1.96] and -2.45kg [-2.83, -2.07], respectively). SGLT-2i treated patients had a significantly more genital infection compared to DPP-4i. On restricting the analysis according to the SGLT-2i FDA-approved dose, only higher doses at ≥52 weeks showed a statistically significant reduction in A1c compared to DPP-4i. On restricting the analysis according to baseline A1c, results favoured DPP-4i if baseline A1c was<8.5%, but favoured SGLT-2i if ≥8.5%. CONCLUSION: While both SGLT-2i and DPP-4i can reduce A1c, SGLT-2i causes a more robust A1c reduction and more weight loss but with more genital infections. Higher doses of SGLT-2i showed more efficacy when compared to DPP-4i; however, this data should be interpreted cautiously given the limited number of trials.
