Abstract
Background
We evaluated the antihyperglycemic efficacy and safety of adding the dipeptidyl dipeptidase-4
inhibitor alogliptin to metformin and sulphonylurea in the treatment of type 2 diabetes
in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care
Trial.
Methods
Patients with type 2 diabetes and recent acute coronary syndrome were randomized to
alogliptin or placebo and standard of care. Participants were followed for up to 40
(median 18) months. In a subgroup taking metformin and sulphonylurea at baseline,
we evaluated change from baseline in glycated hemoglobin (HbA1c), adverse events,
cardiovascular outcomes, laboratory data, and other safety parameters.
Results
There were 1398 patients receiving baseline dual therapy (metformin and sulphonylurea
only) randomized to alogliptin (N = 693) or placebo (N = 705); 550 patients receiving
alogliptin and 505 patients receiving placebo completed the Examination of Cardiovascular
Outcomes with Alogliptin versus Standard of Care without addition of other antihyperglycemic
therapies (P = .008). Changes from baseline to last visit in HbA1c were −0.4% on alogliptin and
+0.1% on placebo (P < .001) in all those with baseline dual therapy and −0.4% for alogliptin and +0.2%
for placebo (P < .001) in those without additional therapies. Reported rates of hypoglycemia were
8.8% for alogliptin and 6.7% for placebo (P = .16). Cardiovascular death and all-cause mortality rates were lower in those receiving
alogliptin compared with those receiving placebo (hazard ratio, 0.49; 95% confidence
interval, 0.28-0.84 and hazard ratio, 0.61; 95% confidence interval, 0.38-0.96, respectively).
Conclusions
Addition of the dipeptidyl peptidase-4 inhibitor alogliptin to dual therapy with metformin
plus sulfonylurea significantly reduced HbA1c and was well tolerated. Lower mortality
rates were seen in patients treated with alogliptin in this subgroup.
Keywords
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References
- ADA Standards of Medical Care in Diabetes.(Available at)http://care.diabetesjournals.org/content/suppl/2015/12/21/39.Supplement_1.DC2/2016-Standards-of-Care.pdfDate accessed: May 6, 2016
- Type 2 diabetes in adults: management (NG28).(Available at)https://www.nice.org.uk/guidance/ng28Date accessed: May 6, 2016
- Comparative effectiveness of adding alogliptin to metformin plus sulfonylurea with other DPP-4 inhibitors in type 2 diabetes: a systematic review and network meta-analysis.Diabetes Ther. 2017; 8: 251-273
- Clinical inertia in people with type 2 diabetes.Diabetes Care. 2013; 36: 3411-3417
- Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.N Engl J Med. 2013; 369: 1317-1326
- Alogliptin after acute coronary syndrome in patients with type 2 diabetes.N Engl J Med. 2013; 369: 1327-1335
- Examination of cardiovascular outcomes with alogliptin versus standard of care in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome.Am Heart J. 2011; 162: 620-626
- 10-year follow-up of intensive glucose control in type 2 diabetes.N Engl J Med. 2008; 359: 1577-1589
- Long-term follow-up after tight control of blood pressure in type 2 diabetes.N Engl J Med. 2008; 359: 1565-1576
- Predisposing factors for any and major hypoglycaemia with saxagliptin versus placebo and overall: analysis from the SAVOR-TIMI 53 Trial.Diabetes Care. 2016; 39: 1329-1337
- Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS.Diabetes Obes Metab. 2017; 19: 1587-1593
- Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: systematic review and meta-analysis.BMJ. 2016; 353: i2231
Article info
Publication history
Published online: March 26, 2018
Footnotes
Funding: Takeda Pharmaceuticals, Inc.
Conflicts of Interest: WBW, SRH, CPC, and RMB were members of the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care Trial Steering Committee and received personal fees from Takeda Pharmaceuticals, Inc, at that time. HH is an employee of Takeda UK Ltd. KK is a consultant to Takeda UK Ltd.
Authorship: All authors had access to the data and played a role in writing this manuscript.
ClinicalTrials.gov Identifier: NCT00968708
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
