: Erection depends largely on the release of nitric oxide (NO) by vascular endothelial cells. Insulin resistance (IR) is a metabolic abnormality that produces endothelial dysfunction characterized by ...decreased synthesis and release of NO. The aim of this paper is to evaluate the effect of treatment with metformin on the response to sildenafil in patients with erectile dysfunction (ED) and IR enrolled in a prospective, randomized, controlled, double‐blind placebo study. We included 30 male patients with ED, IR, and poor response to sildenafil. Exclusion criteria included pharmacologic, anatomic, or endocrine ED; diabetes; prostatic surgery; or chronic illnesses. Erectile function was rated according to the International Index of Erectile Function 5 (IIEF‐5); IR was measured by homeostasis model assessment (HOMA; IR = HOMA ≥ 3). Patients were randomized to receive metformin (n = 17) or placebo (n = 13). After treatment with metformin, patients with ED showed a significant increase in IIEF‐5 score and a significant decrease in HOMA, both occurring at month 2 (IIEF‐5: 17.0 ± 6.0 vs 14.3 ± 3.9, P = .01; HOMA: 3.9 ± 1.6 vs 5.5 ± 2.4, P = .01) to 4 of treatment (IIEF‐5: 19.8 ± 3.8 vs 14.3 ± 3.9, P = .005; HOMA: 4.5 ± 1.9 vs 5.5 ± 2.4, P = .04), with no changes in these parameters in patients with ED receiving placebo. Patients treated with metformin had more adverse events than those who received placebo: 61.5% compared with 7.7%, P = .03, respectively. Adverse events were mild, mainly gastrointestinal, and did not cause discontinuation of treatment. Treatment with metformin in patients with ED and poor response to sildenafil reduced the IR and improved erectile function.
Diabetes mellitus is a true pandemic; type 2 diabetes in particular, with its progressive nature, constitutes a serious health problem. Despite advances and innovations in treatment, it continues to ...generate high morbidity and mortality. Many patients do not achieve their metabolic control objectives, due to clinical inertia, fear of hypoglycaemia, weight gain, the complexity of the treatment and the lack of adherence to it. Recently, the clinical results of the combined use of basal insulin and agonist receptor of the glucagon-like peptide type 1 (AR-GLP1) have been successfully evaluated. Therefore, the combined use of a basal insulin (insulin degludec) with an AR-GLP1 (liraglutide), in a single device (IdegLira), is proposed as an effective and safe therapeutic alternative for the treatment intensification in people with type 2 diabetes. IdegLira has shown greater reductions in HbA1c compared to its individual components, with a low risk of hypoglycaemia and weight loss, both in insulin naïve patients and in those previously insulinized. In this review we describe the pharmacology, the rational of the combination and the most relevant clinical evidence on IdegLira safety and efficacy.
Aim
To assess the associations between baseline glucose‐lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE‐TIMI 58 study.
Materials and methods
...DECLARE‐TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA‐based treatment interaction.
Results
At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase‐4 inhibitors, 750 (4.4%) glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP‐1 RAs (HR 95% CI 0.37 0.18, 0.78 vs. 0.86 0.75, 0.98 in GLP‐1 RA users vs. non‐users, Pinteraction = .03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction > .05). The renal‐specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR 95%CI 0.530.43‐0.66), with no interaction by baseline GLA (Pinteraction > .05). All of these outcomes were similar in those with versus those without baseline metformin use.
Conclusions
The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium‐glucose co‐transporter‐2 inhibitors with GLP‐1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further.
In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 study 17160 patients (pts) with T2DM were randomized to the SGLT2 inhibitor dapagliflozin (DAPA) or placebo (PBO) for a median ...follow up of 4.2 years. At baseline 14068 pts used metformin, 7322 sulfonylureas, 2888 DPP-4 inhibitors, 750 GLP-1 receptor agonist (GLP-1 RA) and 7013 insulin. DAPA reduced the composite of CV death and hospitalization for heart failure (CVD/HHF) vs. PBO regardless of baseline glucose lowering agents (GLA), though the effect appeared to be particularly large in the small group of pts with baseline use of GLP-1 RA (Figure). The overall HR for major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) was 0.93 (95% CI 0.84-1.03) with DAPA vs. PBO, with no interaction by non-insulin GLA, yet a tendency toward greater benefit with DAPA vs. PBO was observed in baseline insulin users (Figure). The renal specific outcome (sustained decrease of ≥40% in eGFR to <60 ml/min/1.73m2, new end stage renal disease, or renal death) was overall reduced with DAPA vs. PBO (HR 0.53, 95% CI 0.43-0.66) with no interaction by baseline GLA (p interaction >0.05). The effects of DAPA on CV and renal outcomes were generally consistent regardless of baseline GLA. Use or non-use of metformin did not alter outcomes. Additional studies defining the clinical benefit of combining CV risk reducing GLAs will be helpful.
Disclosure
A. Cahn: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Consultant; Self; GlucoMe, Medial EarlySign. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. S.D. Wiviott: Consultant; Self; Aegerion Pharmaceuticals, Allergan, Angelmed, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Clinical Research Institute, Bristol-Myers Squibb, Daiichi Sankyo, Eisai Inc., Eli Lilly and Company, ICON Clinical, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Servier, St. Jude Medical, XOMA Corporation. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Amgen, Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eisai Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Other Relationship; Self; See other relationships for list. O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. S. Murphy: Research Support; Self; AstraZeneca. Other Relationship; Self; Abbott, Amgen, Aralez, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, The Medicines Company, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharma. E.L. Goodrich: Other Relationship; Self; AstraZeneca. I. Yanuv: None. A. Rozenberg: None. J. Wilding: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mundipharma International, Napp Pharmaceuticals, Novo Nordisk A/S, Wilmington Healthcare. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. L.A. Leiter: Advisory Panel; Self; Abbott, Amgen, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Amgen, AstraZeneca, Kowa Pharmaceuticals America, Inc., Medicines Company. Speaker’s Bureau; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medscape, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. D.K. McGuire: Consultant; Self; Afimmune, Applied Therapeutics, Merck Sharp & Dohme Corp., Metavant. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Co., Ltd., Eli Lilly and Company, Esperion Therapeutics, Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. L. Litwak: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc., Sanofi. A. Kooy: Advisory Panel; Self; Eli Lilly and Company, Novartis Pharma K.K. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; Daiichi Sankyo, Mundipharma International. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. M. Fredriksson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor Pharmaceuticals, Dyrnamix Inc., Esperion Therapeutics, Inc., IFM Therapeutics, Intarcia Therapeutics, Ionis Pharmaceuticals, Inc., Medicines Company, MedImmune, Merck & Co., Inc. Research Support; Self; Amgen, AstraZeneca, Bayer U.S., Daiichi Sankyo, Eisai Inc., Intarcia Therapeutics, Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis AG, Pfizer Inc., Quark Pharmaceuticals. I. Raz: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Consultant; Self; AstraZeneca, BOL, CamerEyes Ltd, Concenter BioPharma, DarioHealth, Diabot, Exscopia, GlucoMe, Insuline Medical, Medial EarlySIgn, Orgenesis Inc. Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; BOL, CamerEyes Ltd, DarioHealth, Diabot, GlucoMe, Orgenesis Inc.
Introduction
Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking.
Methods
This ...is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015–2016) and the GOAL study conducted in multiple LMICs.
Results
Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c HbA1c ≥ 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5–12 and > 12 years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5–12 years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duration 10.1 ± 6.7 years; 10 LMIC). A significant 2% reduction in mean HbA1c levels was observed after 12 months of treatment. Only 7.2% of participants experienced a symptomatic episode of hypoglycemia (nocturnal or severe hypoglycemia events were infrequent).
Conclusion
The rate of well-controlled participants (HbA1c < 7.0%) in the Wave 7 sub-analysis was lower than that observed in the USA (NHANES survey) or in European countries (GUIDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients’ education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.
Here we report on the impact of completely unpurified islet transplantation on the portal vein pressure (PVP) and the hepatic biochemistry in the peritransplant period and on follow-up. Type I ...diabetic patients underwent simultaneous kidney and islet transplantation. Islets were not purified from the acinar tissue to prevent loss of endocrine mass. Each patient received a mean 521,846 ± 201,539.4 islet equivalents (7812.1 islet equivalents/kg/recipient). Immunosuppression and peritransplant medication were given according to the Giessen protocol. The islets were injected into the left hepatic lobe through the umbilical vein. PVP was recorded at time 0 and every 5 min throughout cell infusion. Liver function was assessed daily for the first 10 days, and on follow-up. Basal, peak, and final PVP were 12 ± 3.8, 25.1 ± 7.9, and 19.5 ± 6.2 mmHg, respectively (basal vs. final, p < 0.05). Bilirubin, alkaline phosphatase, prothrombin time, and APTT stayed within normal range. Peak aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum amylase were 109.4 ± 61.2 IU/L (basal vs. peak, not significant), 79.5 ± 56.9 IU/L (basal vs. peak, not significant), and 887.5 ± 153.6 IU/L (basal vs. peak, p = 0.02), respectively. In all cases AST, ALT, and amylase normalized within 6 days posttransplant and remained so on follow-up (longest control, 33 months posttransplant). Although the intrahepatic infusion of unpurified pancreatic islets affects both the portal vein pressure and the hepatic biochemical profile, this effect is transient and does not compromise the safety of the procedure.
There is a high prevalence of depression in individuals with type 2 diabetes mellitus. Depressive disorders are associated with increased medical morbidity and mortality in individuals with diabetes. ...It has been demonstrated that there is a higher prevalence of diabetic complications among individuals with diabetes and depression compared to those without depression. Several biological alterations have been reported in individuals with depressive disorders, particularly abnormal levels of endocrine-inflammatory markers.This study aims to determine the prevalence of major depressive disorder (MDD) in type 2 diabetes patients, the prevalence of cardiovascular events in individuals with and without MDD and to compare the endocrine-inflammatory profile between groups.
The study was approved by the "Comité de Etica de Protocolos de Investigación del Departamento de Docencia e Investigación del Hospital Italiano de Buenos Aires" with the number "1262" and included only patients who provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Habeas Data law on protection of personal data (Law Nª 25326, Argentina).Type 2 diabetes patients (n = 61) were included and they were classified as having MDD or not according to DSM-IV. Macrovascular disease was obtained from the medical history. Additionally, the intima-media thickness of the common carotid, carotid bifurcations and internal carotid arteries was measured non-invasively by two-dimensional ultrasound imaging. Fasting glucose, fasting lipid profile, inflammatory (CRP, TNF-α) and endocrine (urine free cortisol and saliva cortisol) markers. Student t tests were used to compare means for normally distributed variables and Mann-Whitney test for variables without normal distribution. Relative frequencies were calculated and a chi-square analysis was conducted. Data were expressed as mean ± standard deviation (SD) or median and interquartile range. Multivariable logistic regression was used to determine the relative odds of clinical cardiovascular disease in individuals with compared to those without depression. Differences were considered significant using a two-sided p < 0.05.
21 patients (34%) had MDD and 40 patients (66%) didn't have MDD. Diabetic patients with MDD had significantly higher CRP levels (4.1(1.9-7.6) vs 1.5(0.5-4.4) mg/l; p = 0.02) and 24-hour urine free cortisol (71.4 ± 21.3 vs 59.8 ± 29.3 ug/24 h; p = 0.03). The other metabolic and inflammatory parameters were not statistically different between groups. There was a significantly higher prevalence of cardiovascular events in individuals with MDD: 38% for the depressive group vs 15% for non-depressive group, p = 0.04). Patients with MDD had a 3.5-fold greater odd of having cardiovascular disease.
Diabetic patients with depression are more likely to have cardiovascular events, and different factors can determine this high association.
Insulin and diabetes control in Argentina Gagliardino, Juan J; Costa Gil, José E; Faingold, María C ...
Medicina (Buenos Aires),
2013, Volume:
73, Issue:
6
Journal Article
Peer reviewed
As in the rest of the world, there is a significant gap between scientific knowledge regarding diabetes mellitus and the daily practice outcome, in Argentina. Inadequate diabetes control combined ...with associated cardiovascular risk factors are responsible for an elevated morbid-mortality incidence and the consequent raise in the socioeconomic burden. Some of the factors leading to this situation are the late diagnosis of the disease, the clinical "inertia" (reluctance to prescribe insulin) and the poor education given to the health care team as well as the persons with diabetes. The implementation of a national diabetologic education program targeting health care providers, the persons with diabetes and their families, could contribute to optimize the appropriate insulin prescription, and consequently improve their life quality, while reducing the disease socioeconomic burden. In order to optimize the education program's strategy outcome, insulinization cabinets should be incorporated, the participation of all health systems (public health, social security and private health insurance companies), the media, health sciences, schools and the pharmaceutical industry are needed.
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