Effect of Noninsulin Antidiabetic Drugs Added to Metformin Therapy on Glycemic Control, Weight Gain, and Hypoglycemia in Type 2 Diabetes

Phung, Olivia J; Scholle, Jennifer M; Talwar, Mehak; Coleman, Craig I.

doi:10.1001/jama.2010.405

Cited by 470 publications

(365 citation statements)

References 43 publications

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“…Each new class of noninsulin agents added to the initial treatment lowers A1C by approximately 1% 37. Patients that present with an entry A1C >7.5% should be started on dual therapy from the beginning 38. Those presenting with A1C >9.0% and symptoms would derive greater benefit from adding insulin 39…”

Section: Combination Therapy For Nashmentioning

confidence: 99%

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Alkhouri

Poordad

Lawitz

2018

Hepatology Communications

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Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of insulin resistance, which is the hallmark of type 2 diabetes (T2D). NAFLD is a known risk factor for developing T2D and has a very high prevalence in those with existing T2D. The diabetes spectrum includes several conditions from prediabetes to T2D to insulin‐dependent diabetes leading to macrovascular and microvascular complications. Similarly, NAFLD has a histologic spectrum that ranges from the relatively benign nonalcoholic fatty liver to the aggressive form of nonalcoholic steatohepatitis with or without liver fibrosis to nonalcoholic steatohepatitis‐cirrhosis leading to end‐stage liver disease. The management of T2D has witnessed significant changes over the past few decades with multiple new drug classes entering the treatment algorithm. Unfortunately, there are no U.S. Food and Drug Administration‐approved medications to treat NAFLD, and guidelines for the management of NAFLD are less established. However, the field of drug development in NAFLD has witnessed a revolution over the past 5 years with the establishment of a regulatory pathway for Food and Drug Administration approval; this has generated substantial interest from pharmaceutical companies. Several diabetes medications have been studied as potential treatments for NAFLD with promising results; moreover, drugs that target specific pathways that play a role in NAFLD development and progression are being developed at a rapid pace. Given the similarities between NAFLD and T2D in terms of pathogenesis, underlying risk factors, and disease spectrum, lessons learned from optimizing treatment for T2D can be extrapolated to the management of NAFLD. The aim of this review is to use the founding principles of the comprehensive type 2 diabetes management algorithm to optimize the management of NAFLD. (Hepatology Communications 2018;2:778‐785)

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Section: Combination Therapy For Nashmentioning

confidence: 99%

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Alkhouri

Poordad

Lawitz

2018

Hepatology Communications

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“…Although newer incretin-based therapies offer more options for glycaemic control in T2DM and certain advantages compared with other classical glucose-lowering agents [3,4], the cost of the therapy needs to be taken into account when making global comparisons for clinical use [97]. DPP-4 inhibitors are clearly more expensive than SUs, but less expensive than GLP-1 receptor agonists [98].…”

Section: Pharmacoeconomic Evaluationmentioning

confidence: 99%

“…The mechanism of action of DPP-4 inhibitors is distinct from any existing class of oral glucose-lowering agents [1]. Although they are not more potent in lowering blood glucose concentrations and reducing glycated haemoglobin (HbA 1c ) levels [2], DPP-4 inhibitors nevertheless offer several clinically relevant advantages [3][4][5]. Among the most important benefits are a negligible risk of hypoglycaemia that is considerably lower than that observed with sulphonylurea (SU), and a weight-neutral profile in contrast to the weight gain generally observed with SU and thiazolidinedione (TZD).…”

Section: Introductionmentioning

confidence: 99%

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

Scheen¹

2012

Diabetes & Metabolism

176

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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“…Given that the two major defects in type 2 diabetes are insulin resistance and impaired insulin secretion, metformin is recommended for use in combination with insulin secretogogues and even with intensive insulin therapy [1]. Metformin is now increasingly being used in combination with new incretin-based therapies: glucagon-like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors [4][5][6], both of which enhance pancreatic beta cell function. Interestingly, there have been a few reports suggesting a direct interaction between metformin and the incretin axis [7][8][9].…”

Section: Ampk Amp-activated Protein Kinase Dpp-4mentioning

confidence: 99%

New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser

Cho

Kieffer

2010

Diabetologia

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The two major deficits in type 2 diabetes, insulin resistance and impaired beta cell function, are often treated with metformin and incretin-based drugs, respectively. However, there may be unappreciated benefits of this combination of therapies. In this issue of Diabetologia, Maida et al. (doi:10.1007Maida et al. (doi:10. /s00125-010-1937 report that metformin acutely increases plasma levels of glucagon-like peptide 1 (GLP-1) in mice. Moreover, they show that metformin enhances the expression of the genes encoding the receptors for both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in mouse islets and also increases the effects of GIP and GLP-1 on insulin secretion from beta cells. Interestingly, these incretin-sensitising effects of metformin appear to be mediated by a peroxisome proliferator-activated receptor α-dependent pathway, as opposed to the more commonly ascribed pathway of metformin action involving AMP-activated protein kinase. These provocative findings by Maida et al. extend our understanding of the mechanism of action of metformin and provide further insights into the benefits of combining metformin with incretin-based drugs to combat diabetes.

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Effect of Noninsulin Antidiabetic Drugs Added to Metformin Therapy on Glycemic Control, Weight Gain, and Hypoglycemia in Type 2 Diabetes

Abstract: When added to maximal metformin therapy, all noninsulin antidiabetic drugs were associated with similar HbA(1c) reductions but differed in their associations with weight gain and risk of hypoglycemia.

Cited by 470 publications

References 43 publications

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes

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

New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser

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