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Introduction: Gliptins are a relatively recent class of oral antidiabetic agents used in the treatment of type 2 diabetes. The aim of this study is to identify the adverse effects of gliptins in patients with type 2 diabetes, compare the tolerability of these drugs with data from the literature, and determine patients' behavior in the face of these adverse effects with a view to optimizing their management., Methods: Our study is cross-sectional, descriptive, and analytical, involving 100 patients aged over 20 years, followed at the Endocrinology Department of the Military Hospital Mohammed V., Results: The average age of the patients was 63 years, with a sex ratio F/H of 1.13. The median age of diabetes in the patients was 13 years, with an average blood glucose level of 1.64 and an average hemoglobin A1c of 8.26. The comorbidities were 30% cardiovascular disease, 25% hypertension, and 14% dyslipidemia, and 30% of patients had no comorbidities. Forth-six percent of patients reported adverse events and 54% did not report any adverse event. Twenty-eight percent of the adverse events were gastrointestinal, 18% skin disorders, 14% urinary tract infections, 12% hypoglycemia, 12% nervous system disorders, 8% airway infections, and 8% general disorders., Conclusion: This study shows that gliptins remain a safe option as the side effects seem fairly well tolerated by patients. Adverse events may impact patient compliance and pose a problem of adherence to treatment. Thus, it would be advantageous to develop therapeutic education for diabetic patients to detect and manage adverse effects., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

DPP-4 inhibitors are a well-established treatment for type 2 diabetes. They act by improving glycemic control through the incretin system. This class of molecules are well-tolerated and are associated with a low risk of hypoglycemia. Yet, their efficacy in glycemic control is rather moderate and they don't offer a benefit in terms of cardiovascular or renal protection. Even if they have a good safety profile, it is important to pay attention to the risk of cardiac failure and pancreatitis. This article provides an overview of the use of DPP-4 inhibitors in 2020., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Post-transplantation diabetes (PTDM) exposes to increased morbidity (cardiovascular or infectious complications, early graft dysfunction) and to a risk of premature death. Recognition of risk factors is essential for early and individualized care. The management of a PTDM requires the use of oral antidiabetic treatments (metformin or DPP4 inhibitors) or GLP1 receptor agonists for their favorable effects on weight and kidney that seem ideal in this context. Corticosteroid-induced diabetes or the rare occurrence of diabetic ketoacidosis require insulin therapy. In the long term, the main objective remains to integrate PTDM treatment in a more comprehensive management, targeting the reduction of cardiovascular risk of vulnerable transplant patients., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Type 2 diabetes is a complex disease with an increasing prevalence and a huge morbidity and premature mortality, essentially due to cardiovascular and renal complications. Classical glucose-lowering agents (metformin, sulphonylureas) exert little protective effects on these complications so that emphasis has been put on a multifactorial management targeting all risk factors. Gliptins offer the advantage of an excellent tolerance profile, with no hypoglycaemia or weight gain, but have not shown any specific cardiovascular or renal protection. Over the last decade, new antidiabetic medications (glucagon-like peptide-1 receptor agonists and gliflozins) have demonstrated a cardiovascular and renal protection, independently of glucose control. These data of evidence-based medicine have revolutionized the therapeutic approach of patients with type 2 diabetes who are at high risk of atherosclerotic cardiovascular disease, heart failure and progressive renal disease. Unexpectedly, the protective effect of gliflozins is currently investigated in patients with heart failure or renal disease, in the absence of diabetes.

After metformin monotherapy, the choice between a sulfonylurea and a dipeptidyl peptidase-4 (DPP-4) inhibitor may be critical in clinical practice. This article compares the cardiovascular safety of these two pharmacological classes based on meta-analyses of randomized controlled trials and observational studies. Both approaches show a better cardiovascular safety with DPP-4 inhibitors than with sulfonylureas. However, some heterogeneity exists, most probably explained by differences between the molecules, especially among sulfonylureas as those of last generation (more particularly gliclazide) seem to have a better safety profile. The ongoing head-to-head prospective trial CAROLINA compares the cardiovascular safety of glimepiride and linagliptin in high-risk patients, with results expected in 2019., Competing Interests: L’auteur n’a déclaré aucun conflit d’intérêts en relation avec cet article. Il déclare avoir reçu des honoraires comme orateur, membre d’un conseil scientifique ou investigateur clinicien de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, NovoNordisk, Sanofi, et Servier.

Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are increasingly numerous, especially in the elderly population. Surprisingly, this situation is often under-recognized or even neglected in clinical practice. Yet, most oral antidiabetic (OAD) agents have limitations in case of renal impairment, either because they require a dose reduction, or are contra-indicated mainly for safety reasons. This clinical case gives the opportunity to discuss the modalities of prescription and cautions to be taken when using most commonly prescribed OAD, metformin, insulin secretagogues (sulfonylureas, repaglinide), DPP-4 inhibitors (gliptins) and SGLT2 inhibitors, in a patient with T2D and CKD.

In a patient with type 2 diabetes not well controlled with a basal insulin - metformin combination, several therapeutic options may be considered: intensifying insulin therapy with different schemes (appropriate titration using a more favourable basal insulin analogue, adding one, two or three rapid-acting insulin analogues, shift to two or three premix insulin injections), adding a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of sodium-glucose cotransporters type 2 (gliflozin), or combining a glucagon-like peptide-1 receptor agonist with basal insulin. The choice should be made according the individual profile and preference of the patient, in a personalized approach, taking into account the advantages and disadvantages of each therapeutic solution., Competing Interests: A. Scheen déclare avoir reçu des honoraires comme orateur, membre d’un conseil scientifique ou investigateur clinicien de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, NovoNordisk, et Sanofi. Il a été investigateur clinicien dans les études EMPA-REG OUTCOME, CANVAS-R, TECOS et LEADER. N. Paquot a reçu des honoraires comme orateur de la part des firmes Merck Sharp & Dohme et NovoNordisk.

Because of the natural history of type 2 diabetes and the increasing life expectancy, more and more patients are treated with insulin after failure of oral therapy. International guidelines give the preference to basal insulin, most often while maintaining metformin. If this treatment does not allow to reach the glycaemic objectives, optimizing therapy is mandatory. This clinical case offers the opportunity of discussing both advantages and disadvantages of three therapeutic options : the shift from basal insulin to a basal-plus or a basal-bolus insulin regimen, the addition of another oral glucose-lowering agent, either a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of cotransporters sodium-glucose type 2 cotransporters (gliflozin), or the combination of basal insulin and a glucagon-like peptide-1 receptor agonist.

Two new classes of oral antidiabetic agents play an increasing role in the management of type 2 diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and sodiumglucose cotransporters type 2 (SGLT2) inhibitors (gliflozins). After failure of a monotherapy with metformin (first pharmacological choice in type 2 diabetes), both may offer an alternative to the add-on of a sulphonylurea, especially in patients at risk of hypoglycaemia. However, the choice between a DPP-4 inhibitor and a SGLT2 inhibitor is not easy and should be oriented based upon the individual patient characteristics. The arguments in favour of one or another pharmacological class are discussed, considering a clinical case of a patient with coronary heart disease and type 2 diabetes not well controlled with metformin.

Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycaemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach because the two drugs exert different and potentially complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. Combining the two pharmacological options is safe and does not induce hypoglycaemia. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development., Competing Interests: Le Pr A. J. Scheen déclare avoir reçu des honoraires comme orateur, membre d’un conseil scientifique ou investigateur clinicien de la part des firmes Astra, BMS, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, NovoNordisk, Sanofi, et Takeda. Le Pr N. Paquot a reçu des honoraires comme orateur de la part des firmes Merck Sharp & Dohme et NovoNordisk.

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are more and more prominent medications in the management of type 2 diabetes (T2D), with five molecules commercialized and as many fixed-dose combinations with metformin. After failure of metformin monotherapy, gliptins compete with old medications such as sulphonylureas, on the one hand, or with new oral antidiabetic agents such as inhibitors of renal sodium-glucose cotransporters type 2 (SGLT2) (gliflozines), on the other hand. Another alternative is the use of an incretin mimetic (agonist of glucagon-like peptide-1 receptors, to be injected subcutaneously) rather than an incretin enhancer such as a gliptin, before considering insulin therapy. This article analyses the arguments in favour of DPP-4 inhibitors. We will mainly consider the use of gliptins in patients with recently diagnosed T2D, in elderly and frail patients and in those with chronic kidney disease. To illustrate the discussion, we will analyze the results of both interventional and observational studies with vildagliptin. Obviously, these various groups of patients represent a large proportion of T2D population.

The cardiovascular safety of sitagliptin has been evaluated in TECOS ("Trial Evaluating Cardiovascular Outcomes with Sitagliptin"). TECOS recruited patients with type 2 diabetes and a history of cardiovascular disease who received, as add-on to their usual therapy, either sitagliptin (n = 7.257) or placebo (n = 7.266), with a median follow-up of 3 years. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% confidence interval, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). The cardiovascular safety of sitagliptin, which was already shown in meta-analyses of phase II-III randomised controlled trials and in observational cohort studies in real life, is now confirmed in the landmark prospective cardiovascular outcome study TECOS.

The cardiovascular safety of dipeptidyl peptidase-4 inhibitors (gliptins) has been well studied. Favourable effects of these oral antidiabetic agents have been reported in meta-analyses of phase II-III randomised controlled trials. Three large prospective trials, which were specifically designed to investigate cardiovascular safety, showed non-inferiority of saxagliptin (SAVOR-TIMI 53), alogliptin (EXA-MINE) and sitagliptin (TECOS) versus placebo as far as major cardiovascular events are concerned, including mortality. The suspected increase in the rate of hospitalisation due to congestive heart failure reported in SAVOR-TIMI 53 was neither found in EXAMINE nor recently confirmed in TECOS. Direct comparative trials, evaluating not only safety but also efficacy, with other oral antidiabetic medications would be of major interest.

Who never had a type 2 obese diabetic patient, treated by several oral antidiabetic drugs and insulin, with consequent weight gain associated with the therapeutic escalation and uncontrolled diabetes? The arrival of GLP-1 agonists and SGLT-2 inhibitors allows to reevaluate the management of these patients, with their favorable effects on glycemic control, weight and the risk of hypoglycemia and their complementary mechanisms to conventional treatments. The vicious cycle of weight gain and increased need of insulin is limited. The choice between these two molecules must be based on several factors (glycemic target, weight, comorbidities, route of administration, side effects, etc.), and the balanced enthusiasm of these new treatments with the insufficient data regarding their long-term safety and their impact on micro- and macrovascular complications.

Type 2 diabetes is characterised by insulin resistance and deficiencywhich explains the multitude of molecules developed for its treatment.The beneficial effects of metformin and sulfamides have been demonstrated. Over the last 10 years, new molecules have appeared: acarbose, repaglinide and incretins.

The pharmacological therapy of hyperglycaemia in type 2 diabetes becomes increasingly complex. After failure of metformin monotherapy, several choices are possible. In clinical practice, the most common dilemma is to choose between adding a sulphonylurea or adding a dipeptidyl peptidase-4 inhibitor (gliptin). This review analyses the arguments in favour of one or the other pharmacological option, based upon criteria of efficacy, tolerance, safety, easiness of use, use in at risk populations and, last but not least, cost of therapy. In general, a patient-centered approach is recommended with an individualization of the therapy in function of the characteristics of each patient with the aim to obtain the best benefits/ risks ratio, at an affordable cost.

Alogliptin (Vipidia) is a new selective inhibitor of dipeptidyl peptidase-4. By potentiating insulin secretion and by inhibiting glucagon secretion, both in a glucose-dependent manner, it improves glucose control of type 2 diabetic patients, without increasing the risk of hypoglycaemia and inducing weight gain, with an excellent clinical and biological tolerance. Both efficacy and safety have been demonstrated in randomised controlled trials, in monotherapy or in combination with other oral antidiabetic agents or even insulin. These results were obtained independently of clinical or demographic patient characteristics, including in elderly subjects and in patients with renal insufficiency. However, because alogliptin is eliminated through the kidneys, the usual dose of 25 mg once daily should be reduced to 12.5 mg per day in case of moderate renal impairment and to 6.25 mg per day in case of severe renal failure. Cardiovascular safety of alogliptin has been demonstrated in a large prospective study (EXAMINE) showing non-inferiority versus placebo in type 2 diabetic patients following an acute coronary syndrome.

Type 2 diabetes is characterized by an insulin secretory defect that cannot compensate for insulin resistance. Such relative defect is present in the fasting state (insufficient basal insulin levels) and contributes to overnight hyperglycaemia; it is even more pronounced in the postprandial state when it is then the main responsible factor for hyperglycaemia following meals. An original approach to correct these two disturbances is to propose a therapy combining the injection of a basal insulin (most commonly at bedtime to better control fasting glycaemia) and the administration of an incretin-based medication to potentiate insulin response to the three main meals, without inducing hypoglycaemia. This latter effect can be obtained either by blocking the degradation of incretin hormones with an oral inhibitor of dipeptidyl peptidase-4 (gliptin), or by injecting an agonist of glucagon-like peptide-1 (GLP-1) receptors. These basal insulin-incretin combined therapies are well validated in various controlled trials and observational studies. Lixisenatide is the first GLP-1 receptor agonist being reimbursed in this specific indication of combination with basal insulin in Belgium.

Sitagliptin (Januvia) was the first selective inhibitor of dipeptidyl peptidase-4 commercialized for the management of type 2 diabetes. It is also available as a fixed-dose combination with meformin (Janumet). Almost 5 years after its launch in Belgium, the present review summarizes the most recent data regarding the clinical efficacy of this antidiabetic agent, the controversy about its safety profile, its use at lower dosage in case of moderate to severe renal insufficiency, the various indications that have been successively accepted and reimbursed, and, finally, the perspectives offered by a large ongoing cardiovascular outcome trial (TECOS).

Once lifestyle measures implemented, if hyperglycemia persists, above individual HbA1c targets, a medication should be started in type 2 diabetic patients (T2DM). First, unless exception, an oral antidiabetic drug. Except in case of intolerance, the initial monotherapy, metformin remains the strengthening treatment. Latter, combination of two oral drugs, now offers several options, mainly the choice to associate a "conventional insulin-secretor", sulfonylureas, glinide, or a "new one" belonging the class of "incretin", more readily a gliptine (DPP-4 inhibitors) rather than injectable GLP-1 analogue which can also be sometimes chosen at this stage. These options are mostly new and have the advantage a neutral or favourable (for GLP-1) effect on body weight in obese type 2 DM patient and the absence of any hypoglycaemic risk in both classes of incretins. But this risk varies depending on the patient profile, much higher if the target HbA1c is low (6 to 6.5 or 7%), or in the elderly, fragile and/or in case of renal insufficiency. These two different situations with a high risk of hypoglycaemia, define best indications of this new class. If dual oral therapy does not achieve the goals we are faced with three options: triple oral therapy: metformin-sulfonylurea-gliptine or one of two approaches with injections, insulin or GLP-1 analogues. The use of GLP-1 analogues is often delayed today and put wrongly in balance with the transition to insulin, a use already delayed in France and insufficient. The use of incretins is new and needs to be validated by studies of sustainability on glycemic control, prevention of microvascular and macrovascular complications and after years on the market security of use, primarily on the exocrine pancreas. In short, individualization of strategies and HbA1c targets are required, the new molecules can help us in this process. This individualization can easily be done through the handy guide proposed by the experts ADA EASD statement, endorsed by the SFD, abandoning the complex algorithm recently again proposed by HAS and ANSM in 2013. A recommendation that prioritizes the costs of the strategies. An absolutely critical issue, while admitting not to have the tools to measure them in all their dimensions. Finally, we must reconsider every treatment after a maximum of 6 months of use, if the results are deemed inadequate substitute rather than adding drugs., (Copyright © 2013. Published by Elsevier Masson SAS.)

People with chronic kidney disease (CKD) of stages 3-4 (creatinine clearance <50 ml/min) represent 25-30% of type 2 diabetic patients, but the problem is often underrecognized or neglected in clinical practice. However, most of oral antidiabetic agents have limitations in case of renal impairment, either because they require a dose adjustment, or because they are contra-indicated for safety reasons. It is the case for metformin (risk of lactic acidosis) and for most sulfonylureas (risk of hypoglycaemia). New antidiabetic agents are better tolerated in case of CKD. However, the daily dose of dipeptidyl peptidase-4 inhibitors should be adjusted (except for linagliptin). Concerning new inhibitors of renal SGLT2 cotransporters, they have a reduced efficacy and their safety remains to be demonstrated in presence of CKD.

Sitagliptin (Januvia), the first selective inhibitor of dipeptidylpeptidase-4 with a so-called incretin effect, has been evaluated in SUGAR, a large Belgian prospective observational study carried out in general practice. Sitagliptin, at a dose of 100 mg once daily, was added to previous treatment of not well controlled type 2 diabetic patients (> 95% on metformin monotherapy). Among 605 patients analysed in intention to treat, the worse the glycaemic control at entry, the greatest the reduction in glycated haemoglobin (HbA1c) and fasting plasma glucose levels after the addition of sitagliptin (p < 0.001). No specific factor was associated with the quality of initial glucose control among age, body mass index, the duration of diabetes or the modalities of its pharmacological treatment. Similarly, among these factors, none was significantly associated with the reduction in HbA1c or fasting plasma glucose levels observed with the addition of sitagliptin. Thus, sitagliptin was as active in older as in younger subjects, in obese as in nonobese people and in patients with diabetes of long versus short duration. In particular, SUGAR recruited data on 191 patients above 70 years in whom sitagliptin was as effective and safe as in younger patients with type 2 diabetes.

The increase in prevalence and the particularities of care in old diabetic patients, which accumulate consequences of both, age and diabetes, the treatment must be well tolerated. The main adverse event is a hypoglycemia risk because of its major consequences for the elderly diabetic subjects. Since few years, three dipeptydil-peptidase-4 inhibitors (DPP-4), for which some studies have included type 2 diabetic old subjects are available in Europe. Their efficiency and their tolerance do not differ significantly from those noted at the younger diabetics. The reduced risk of hypoglycemia and the absence of influence on the weight are two interesting arguments to use them in the old diabetic patients. It remains however necessary to realize studies led specifically to old and even oldest subjects, corresponding to those in daily practice. If the data on their tolerance is confirmed, it could intend to revise therapeutic target for the old diabetic patients.

Sitagliptin (Januvia), the first selective inhibitor of dipeptidylpeptidase-4, has been assessed in a large Belgian prospective observational study. The aim of the SUGAR study was to evaluate the efficacy of sitagliptin, at a dose of 100 mg once daily, when it was added in patients with uncontrolled type 2 diabetes followed in real life conditions. In the intent-to-treat population (n = 605), mean glycated haemoglobin level decreased from 8.41 +/- 1.18% to 7.29 +/- 0.86% after a follow up averaging 110 days (p < 0.0001). Similarly, mean fasting plasma glucose level decreased from 180 +/- 50 mg/dl to 141 +/- 37 mg/ dl (p < 0.0001). The improvement of these two parameters was observed independently of basal demographic characteristics, but was directly influenced by baseline initial corresponding values. The vast majority of patients included in SUGAR were initially treated by metformin as monotherapy (current criterion for sitagliptin reimbursement in Belgium); metformin daily dose slightly decreased when sitagliptin was added (from 1975 +/- 681 mg to 1919 +/- 667 mg; p = 0.033). Patients receiving other glucose-lowering agents, as single or combined therapies, had also a significant alleviation of their treatment when sitagliptin was added. After 3-6 months of follow up, more than 95% of patients still received sitagliptin, arguing for both the efficacy and the good tolerance of this new oral antidiabetic agent in clinical practice.