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Effetti sulla variabilità glicemica e sul compenso glico-metabolico di metformina, pioglitazone e sitagliptin in pazienti affetti da diabete mellito di tipo 2
Full text linkScopo: il trattamento del diabete mellito di tipo 2 richiede spesso l'uso di più agenti ipoglicemizzanti per raggiungere un adeguato controllo glicemico. Scopo di questo studio è stato valutare gli effetti di una triplice terapia con metformina, pioglitazone e sitagliptin sul controllo glicemico e la variabilità glicemica rispetto a metformina e metformina + pioglitazone. Per valutare la variabilità glicemica è stato utilizzato un sistema di monitoraggio glicemico in continuo della glicemia.
Materiali e Metodi: sono stati arruolati 66 diabetici di tipo 2 non ben controllati. I pazienti hanno assunto per tre mesi metformina 500 mg tre volte al giorno, a cui è stato, poi, aggiunto pioglitazone 15 mg due volte al giorno per altri tre mesi ed, infine, sitagliptin 100 mg, una volta al giorno, per ulteriori tre mesi. Ad ogni fase dello studio, se il paziente raggiungeva l'obiettivo di emoglobina glicata (HbA1c) desiderato (<6.5%), veniva fatto uscire dallo studio. Abbiamo valutato: l'HbA1c, la glicemia a digiuno (FPG), la glicemia post-prandiale (PPG), l'insulinemia a digiuno (FPI), l'indice HOMA (HOMA-IR), la proteina C-reattiva ad alta sensibilità (hs-CRP), il profilo lipidico, la lipoproteina (a) [Lp(a)], la metalloproteinasi-2 (MMP-2), la metalloproteinasi-9 (MMP-9), le molecole di adesione (sICAM-1, sVCAM-1), la sE-selectina, l'adiponectina (ADN).
Risultati: abbiamo registrato una significativa riduzione di HbA1c, FPG, e PPG con metformina + pioglitazone (p < 0.05 vs basale), ed un’ulteriore riduzione con metformina + pioglitazone + sitagliptin (p < 0.01 vs basale). Abbiamo osservato un miglioramento del profilo lipidico rispetto al basale con metformina + pioglitazone + sitagliptin (p < 0.05 vs basale). C'è stata una riduzione di Hs-CRP, sICAM-1, sVCAM-1, ed un aumento di ADN con metformina + pioglitazone (p < 0.05 vs basale) e con metformina + pioglitazone + sitagliptin (p < 0.01 vs basale). i livelli di eSelectina si sono ridotti solo con metformina + pioglitazone + sitagliptin (p < 0.05 vs basale). Per quanto riguarda la variabilità glicemica, la deviazione standard è risultata minore con metformina + pioglitazone (p < 0.05 vs basale) e con metformina + pioglitazone + sitagliptin (p < 0.01 vs basale). Il valore M, indice di variabilità glicemica, è risultato più basso con metformina + pioglitazone + sitagliptin.
Conclusioni: la combinazione di metformina + pioglitazone + sitagliptin è risultata efficace nel migliorare il controllo glicemico e nel ridurre la variabilità glicemica e potrebbe essere un'opzione per il trattamento del diabete mellito di tipo 2.Background and aim: the treatment of type 2 diabetes mellitus often requires the use of one or more hypoglycemic agents to reach the adequate glycemic control. The aim of the study is to evaluate the effects of a triple therapy with metformin, pioglitazone and sitagliptin on glycemic variability compared to metformin monotherapy, and compared to a combination of metformin and pioglitazone. To assess glycemic variability a continuous glucose monitoring system was used. Material and Methods: we enrolled 66 not well controlled, type 2 diabetic patients. Patients were instructed to take metformin 500 mg three times a day for the first three months, then pioglitazone 15 mg twice a day was added for further three months, and finally sitagliptin 100 mg once a day was added for the last three months. At the baseline, and every three months a continuous glucose monitoring system was performed. At any stage of the study, if the value of glycated hemoglobin reached the desired goal (<6.5%), participation in the study was interrupted. We assessed: glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial glucose (PPG), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), lipid profile, lipoprotein (a) [Lp(a)], metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9), soluble adhesion molecules (sICAM-1, sVCAM-1), sE-selectin, adiponectin (ADN).
Results: we recorded a significant decrease of HbA1c, FPG, and PPG with metformin + pioglitazone (p < 0.05 vs baseline), and a further decrease with metformin + pioglitazone + sitagliptin (p < 0.001 vs baseline). There was an improvement of lipid profile compared to baseline with metformin + pioglitazone + sitagliptin (p < 0.05 vs baseline). We recorded a decrease of Hs-CRP, sICAM-1, sVCAM-1, and an increase of ADN with metformin + pioglitazone (p < 0.05 vs baseline), and with metformin + pioglitazone + sitagliptin (p < 0.01 vs baseline). A decrease of eSelectin was recorded only with metformin + pioglitazone + sitagliptin (p < 0.05 vs baseline). Regarding glycemic variability, standard deviation was lower with metformin + pioglitazone (p < 0.05 vs baseline), and metformin + pioglitazone + sitagliptin (p < 0.01 vs baseline). The M value, an index of glycemic variability, was lower with metformin + pioglitazone + sitagliptin (p < 0.05 vs baseline).
Conclusion: combination of metformin + pioglitazone + sitagliptin proved to be effective in improving glycemic control, and in decreasing glycemic variability, therefore it could be suitable for the treatment of type 2 diabetic patients
Assessment and management of left ventricular hypertrophy in type 2 diabetes patients with high blood pressure
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Effects of thiazolidinediones and sulfonylureas in patients with diabetes
No full textIn the current literature there are different opinions about the use of thiazolidinediones or sulfonylureas. Some authors have reported that thiazolidinediones increase total body glucose disposal and reduce hepatic glucose production, reducing both peripheral and hepatic insulin resistance (or enhances both peripheral and insulin sensitivity). They consider thiazolidinediones a better drug compared to sulfonylureas because they do not induce hypoglycemia and they provide a protection for the pancreatic beta-cell. On the other side, some authors have reported that the improved glycemic control obtained with thiazolidinedione use is associated with an increase in body weight and a worsening of lipid profile, and they also warn providers to consider the potential for serious adverse cardiovascular effects of the treatment with rosiglitazone for type 2 diabetes mellitus, negating some of the benefits of the improved metabolic control. They have also reported that sulfonylureas are safer compared to thiazolidinediones because they give a better and faster improvement of glycated hemoglobin without giving the adverse effects reported with the use of thiazolidinediones. Considering the emerging discrepancies from these studies we decided to undertake a thorough literature search on Medline and Embase to evaluate the effects of thiazolidinediones and sulfonylureas in people with diabetes. In particular, this review examines the effects and the rationale and practicalities for the use of sulfonylureas or thiazolidinediones, alone and in combination therapy with other antidiabetes drugs, to treat type 2 diabetes mellitus considering, as primary end points, glycated hemoglobin, fasting plasma glucose, fasting plasma insulin, homeostasis model assessment indices, body weight, body mass index, blood pressure, and, when available, data on lipid profile. We also evaluated the effects of these two drugs on beta-cell function, insulin resistance, and inflammatory markers, also recording the frequency of adverse events such as edema and heart failure
Optimizing glycemic control: clinical utility of exenatide prolonged release injection
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