Effect of adding sitagliptin, a dipeptidyl peptidase‐4 inhibitor, to metformin on 24‐h glycaemic control and β‐cell function in patients with type 2 diabetes

Brazg, Ronald; Xu, Libo; Man, Chiara Dalla; Cobelli, Claudio; Thomas, Kenneth A.; Stein, Peter

doi:10.1111/j.1463-1326.2006.00691.x

Cited by 136 publications

(117 citation statements)

References 14 publications

(18 reference statements)

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“…The improved islet function by sitagliptin results in reduction of both fasting glucose and prandial glucose as revealed in different studies in subjects with type 2 diabetes. 25,36,48,49 In fact, the entire 24-hour glucose profile is reduced by sitagliptin, as is evident from a study examining addition of sitagliptin to ongoing metformin therapy compared to metformin treatment alone (Figure 2). …”

Section: Mechanisms Of Actionmentioning

confidence: 94%

“…[21][22][23] These actions reduce both fasting and prandial glucose levels and the 24-hour glucose profile, as has been shown for NVP-DPP728 and sitagliptin. 24,25 Rodent studies have also shown that DPP-4 inhibitors (vildagliptin and sitagliptin) increase islet mass and normalize islet cell topography in diabetes models in mice. 26,27 This would suggest that DPP-4 inhibition targets the important islet dysfunctions in type 2 diabetes.…”

Section: Incretin-based Therapymentioning

confidence: 99%

“…[36][37][38][39][40][41][42][43][44][45][46] Improved β-cell function is also evident from reduced proinsulin to insulin ratio. 38,[41][42][43][44]47 Sitagliptin also reduces glucagon levels, 25,30 although this needs to be examined in more detail. The improved islet function by sitagliptin results in reduction of both fasting glucose and prandial glucose as revealed in different studies in subjects with type 2 diabetes.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

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Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

Åhrén¹

2010

DMSO

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Inhibition of dipeptidyl peptidase-4 (DPP-4) prevents the inactivation of glucagonlike peptide-1 (GLP-1). This increases circulating levels of active GLP-1, stimulates insulin secretion and inhibits glucagon secretion, which results in lowering of glucose levels and improvement of the glycemic control in patients with type 2 diabetes. This review summarizes experiences with DPP-4 inhibition in the treatment of type 2 diabetes, with a focus on sitagliptin. Sitagliptin has in several clinical studies been shown to improve metabolic control in type 2 diabetes, both when used as monotherapy and when used in combination with metformin, sulfonylurea, thiazolidinediones or insulin. The reduction in HbA 1c is ≈0.6% to 1.0% from baseline levels of 7.5% to 8.7% over 6 to 12 months therapy. Sitagliptin has a favorable safety profile, is highly tolerable, and there is a minimal risk of hypoglycemia. Furthermore, sitagliptin is body weight neutral or induces a slight body weight reduction. Sitagliptin may be used in the early stages of type 2 diabetes in combination with metformin or other treatments in subjects with inadequate glycemic control on these treatments alone. Sitagliptin may also be used in monotherapy and, finally, sitagliptin may be used in combination with insulin in more advanced stages of the disease.

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Section: Mechanisms Of Actionmentioning

confidence: 94%

Section: Incretin-based Therapymentioning

confidence: 99%

Section: Mechanisms Of Actionmentioning

confidence: 99%

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Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

Åhrén¹

2010

DMSO

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“…50 Improved glycaemic control has been observed with regimens involving combinations of metformin and the GLP-1 analogues, exenatide [51][52][53][54][55][56][57][58] and liraglutide, 59,60 or the DPP-4 inhibitors, vildagliptin 61,62 or sitagliptin. 26,[63][64][65][66] The additive antihyperglycaemic efficacy of these combinations relates to different cellular modes of action of metformin compared with each of the other classes of agents.…”

Section: Metformin In Combinationmentioning

confidence: 99%

Metformin therapy and clinical uses

Scarpello

Howlett

2008

Diabetes and Vascular Disease Research

287

225

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Metformin is now established as a first-line antidiabetic therapy for the management of type 2 diabetes. Its early use in treatment algorithms is supported by lack of weight gain, low risk of hypoglycaemia and its mode of action to counter insulin resistance. The drug's anti-atherosclerotic and cardioprotective effects have recently been confirmed in prospective and retrospective studies, and appear to reflect a collection of glucose-independent effects on the vascular endothelium, suppressant effects on glycation, oxidative stress and formation of adhesion molecules, stimulation of fibrinolysis and favourable effects on the lipid profile. Although avoidance of troublesome gastrointestinal tolerability issues requires careful dose titration, the risk of serious adverse events is considered low provided that contra-indications (especially with respect to renal function) are observed. As many of its actions go beyond glucose lowering, emerging evidence indicates potential benefits in other insulin-resistant states and possibly tumour suppression.

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“…21 Patients had diabetes for an average duration of 6.6 years, with average initial HbA1c level of 7.7% and average fasting plasma glucose level of 8.4 mmol/L. In a long-term study on the effect of sitagliptin as add-on therapy to metformin in subjects with inadequate glycemic control, sitagliptin (100 mg once daily) was added to metformin (1.5 g daily) for 24 weeks.…”

Section: Randomized Clinical Trial Sitagliptin As Add-on Therapy To Mmentioning

confidence: 99%

Combination treatment for type 2 diabetes mellitus (T2DM): dipeptidyl peptidase-4 inhibitors (DPP-4) and metformin

Kristin

2017

JMedScie

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Using the concept of inhibition of dipeptidyl peptidase-4 (DPP-4) as a new treatment for type 2 diabetes mellitus (T2DM) is based on the inhibition of bioactive peptide inactivation process. Most clinical trials on DPP-4 inhibition are based on vildagliptin, sitagliptin, saxagliptin, and linagliptin. The drugs may improve glycemic control when they are given as a combination with other oral hyperglycemic agents or when they are given to patients who received metformin and still had inadequate glycemic control. Studies showed that vildagliptin was well-tolerated if it was given as add-on treatment to metformin for 24 weeks duration. In addition, vildagliptin showed significant clinical improvement proven by the associated decrease in HbA1c and fasting glucose levels. Sitagliptin in initial combination therapy with metformin decreased HbA1c level by 2.1% after 24 weeks of treatment. It was reported that DPP-4 inhibitor saxagliptin increased glycemic control when it was added to metformin. The study included 743 patients with an average HbA1c level of 8.0% when they were treated with metformin alone. After 24 weeks of treatment, saxagliptin decreased HbA1c level by 0.7%. A multicenter, randomized, placebo-controlled, double-blind, parallel-group study examined the efficacy and tolerability of linagliptin as treatment adjunctive to metformin in patients T2DM. The primary end point was changed in HbA1c from baseline to 24 weeks of treatment. The mean adjusted change from baseline in HbA1c in the linagliptin group was 0.49% compared with an increase of 0.15% in the placebo group, with 26% and 9% of participants in the linagliptin and placebo groups, respectively, achieving an HbA1c 7.0% at 24 weeks. The combination of DPP-4 inhibitors and metformin has been shown to be well-tolerated with a very low risk of hypoglycemia. Therefore, DPP-4 inhibitors and metformin combination is an efficient, safe, and well-tolerated therapy for T2DM. ABSTRAKKonsep penghambatan terhadap dipeptidyl peptidase-4 (DPP-4) sebagai obat baru untuk diabetes mellitus tipe 2 (DMT2) didasarkan pada penghambatan proses inaktivasi peptida bioaktif. Sebagian besar uji klinis penghambat DPP-4 dilakukan menggunakan vildagliptin, sitagliptin, saxagliptin, dan linagliptin. Obat tersebut dapat memperbaiki kontrol glikemik jika diberikan dalam kombinasi dengan antidiabetes oral lainnya atau jika diberikan kepada pasien yang menerima metformin dan kontrol glikemik tidak memadai. Uji klinik menunjukkan bahwa vildagliptin dapat ditoleransi dengan baik jika diberikan sebagai J Med Sci, Volume 49, No. 3, 2017 July: 141-151 142 obat tambahan pada metformin selama 24 minggu. Selain itu vildagliptin menunjukkan perbaikan klinis bermakna yang dibuktikan dengan penurunan HbA1c dan kadar glukosa puasa. Sitagliptin sebagai obat tambahan pada metformin menurunkan HbA1c sebesar 2,1% setelah 24 minggu pengobatan. Dilaporkan bahwa penghambat DPP-4 saxagliptin sebagai obat tambahan pada metformin meningkatkan kontrol glikemik. Penelitian ini melibatkan 743 pasie...

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Effect of adding sitagliptin, a dipeptidyl peptidase‐4 inhibitor, to metformin on 24‐h glycaemic control and β‐cell function in patients with type 2 diabetes

Abstract: In this study, the addition of sitagliptin 50 mg b.i.d. to ongoing metformin therapy improved 24-h glycaemic control and beta-cell function, and was generally well tolerated in patients with type 2 diabetes.

Cited by 136 publications

References 14 publications

Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

Metformin therapy and clinical uses

Combination treatment for type 2 diabetes mellitus (T2DM): dipeptidyl peptidase-4 inhibitors (DPP-4) and metformin

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