Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes*

Scott, Russell S.; Loeys, Tom; Davies, Melanie J.; Engel, Samuel S.

doi:10.1111/j.1463-1326.2007.00839.x

Cited by 211 publications

(186 citation statements)

References 27 publications

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“…For the effects of adding sitagliptin we have two useful trials with HbA 1c baseline 7.7% and 7.8%, which reported reductions in HbA 1c of 0.67% and 0.79% (Scott 2007, 176 Nauck 2007 177 ) giving a mean of 0.73%.…”

Section: Nma Of Sodium-glucose Co-transporter 2 Inhibitors and Comparmentioning

confidence: 99%

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Johnston

Uthman

Cummins

et al. 2017

Health Technol Assess

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Background Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium–glucose co-transporter 2 (SGLT2) inhibitors. Objective To review the clinical effectiveness and cost-effectiveness of dapagliflozin (Farxiga, Bristol-Myers Squibb, Luton, UK), canagliflozin (Invokana, Janssen, High Wycombe, UK) and empagliflozin (Jardiance, Boehringer Ingelheim, Ingelheim, Germany/Eli Lilly and Company, Indianapolis, IN, USA), in monotherapy in people who cannot take metformin. Sources MEDLINE (1946 to February 2015) and EMBASE (1974 to February 2015) for randomised controlled trials lasting 24 weeks or more. For adverse events, a wider range of studies was used. Three manufacturers provided submissions. Methods Systematic review and economic evaluation. A network meta-analysis was carried out involving the three SGLT2 inhibitors and key comparators. Critical appraisal of submissions from three manufacturers. Results We included three trials of dapagliflozin and two each for canagliflozin and empagliflozin. The trials were of good quality. The canagliflozin and dapagliflozin trials compared them with placebo, but the two empagliflozin trials included active comparators. All three drugs were shown to be effective in improving glycaemic control, promoting weight loss and lowering blood pressure (BP). Limitations There were no head-to-head trials of the different flozins, and no long-term data on cardiovascular outcomes in this group of patients. Most trials were against placebo. The trials were done in patient groups that were not always comparable, for example in baseline glycated haemoglobin or body mass index. Data on elderly patients were lacking. Conclusions Dapagliflozin, canagliflozin and empagliflozin are effective in improving glycaemic control, with added benefits of some reductions in BP and weight. Adverse effects are urinary and genital tract infections in a small proportion of users. In monotherapy, the three drugs do not appear cost-effective compared with gliclazide or pioglitazone, but may be competitive against sitagliptin (Januvia, Merck Sharp & Dohme Limited, Kenilworth, NJ, USA). Funding The National Institute for Health Research Health Technology Assessment programme.

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Section: Nma Of Sodium-glucose Co-transporter 2 Inhibitors and Comparmentioning

confidence: 99%

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Johnston

Uthman

Cummins

et al. 2017

Health Technol Assess

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“…However, in the present review, only head-to-head trials vs active comparators are presented in brief. Gliptins have also been compared with SUs (glimepiride, glipizide, gliclazide) [27][28][29][30][31][32][33][34], TZDs (pioglitazone 30 mg, rosiglitazone 8 mg) [35][36][37][38][39] and GLP-1 receptor agonists (exenatide, liraglutide) [36,40,41]. However, only one head-to-head study compared two different DPP-4 inhibitors in the same trial: saxagliptin 5 mg with sitaglitptin 100 mg as add-ons to basal metformin therapy [42].…”

Section: Gliptins Combined With Metforminmentioning

confidence: 99%

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

Scheen¹

2012

Diabetes & Metabolism

174

124

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Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA 1c reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA 1c reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA 1c when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA 1c and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-tohead trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials. Keywords:Clinical trial-DPP-4 inhibitor; Alogliptin; Linagliptin; Saxagliptin; Sitagliptin; Vildagliptin; Type 2 diabetes mellitus; Review Résumé Les inhibiteurs de la DPP-4 dans le traitement du diabète de type 2 : revue critique des essais cliniques contrôlés.Les inhibiteurs de la dipeptidylpeptidase-4 (DPP-4) offrent de nouvelles options pour le traitement du diabète de type 2. Des comparaisons directes avec d'autres médicaments antidiabétiques chez des patients naïfs de tout traitement ont démontré que les inhibiteurs de la DPP-4 étaient un peu moins puissants pour diminuer ...

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“…In general, the changes in HbA 1c changes recapitulated the approximate glucoselowering effect of these drugs as monotherapy. Such studies, therefore, provide little insight into metformin itself, other than the observation that these respective combinations are effective, well tolerated and without any substantial added risk of hypoglycaemia [19][20][21][22][23][24][25]. Other investigations have examined initial combination therapy, mainly in treatmentnaive individuals; these have further reinforced the concept that combining two drugs with distinct mechanisms of action leads to greater glucose-lowering potential than the constituents alone [23], allowing patients to better achieve HbA 1c targets.…”

Section: Metformin and Dpp-4 Inhibitors Glp-1 Receptor Agonists And mentioning

confidence: 99%

Metformin: clinical use in type 2 diabetes

2017

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Efficacy and safety of sitagliptin when added to ongoing metformin therapy in patients with type 2 diabetes*

Abstract: In this 18-week study, the addition of sitagliptin was effective and well tolerated in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Treatment with sitagliptin produced similar reductions in HbA(1c) compared with the addition of rosiglitazone.

Cited by 211 publications

References 27 publications

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials

Metformin: clinical use in type 2 diabetes

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