Relationship of body mass index with efficacy of exenatide twice daily added to insulin glargine in patients with type 2 diabetes.

This post hoc analysis assessed the evidence behind common reimbursement practices by evaluating the relationship of body mass index (BMI) ranges (<30, 30-35 and >35 kg/m(2) ) with treatment effects of exenatide twice daily among patients with type 2 diabetes. Patients received exenatide twice daily added to insulin glargine in two 30-week studies (exenatide twice daily vs insulin lispro, n = 627; exenatide twice daily vs placebo, n = 259). No association of baseline BMI with changes in efficacy variables was observed. Glycated haemoglobin (HbA1c) reductions were significant (p < 0.0001) and similar across BMI range groups in the lispro-comparator study and greater for exenatide versus placebo in the placebo-controlled study. Significant weight loss occurred with exenatide across BMI range groups (p < 0.0001), while weight increased with both comparators. Achievement of HbA1c <7.0% (<53 mmol/mol) without weight gain was greater for exenatide versus comparators. Systolic blood pressure decreased across BMI range groups with exenatide in the lispro-comparator study (p < 0.0001); changes in lipids were not clinically meaningful. Minor hypoglycaemia was less frequent for exenatide versus insulin lispro. These findings suggest that BMI alone should not limit clinical decision-making or patient access to medication.

Efficacy and safety of linagliptin as add-on therapy to basal insulin and metformin in people with Type 2 diabetes.

AIM: To evaluate the efficacy and safety of linagliptin in people with Type 2 diabetes inadequately controlled on basal insulin and metformin. METHODS: This was a post hoc subanalysis of participants who received basal insulin and metformin in a global phase III study that randomized participants (1:1) to receive linagliptin 5 mg once daily or placebo for ≥52 weeks as add-on therapy to basal insulin alone or in combination with metformin and/or pioglitazone. During the first 24 weeks, the background dose of basal insulin remained stable; thereafter, adjustments based on glucose concentrations were recommended. The primary endpoint of the subanalysis was the change from baseline in HbA1c after 24 weeks. The safety analysis incorporated data up to a maximum of 110 weeks. RESULTS: A total of 950 participants receiving background insulin and metformin were included in this subanalysis (linagliptin and placebo, both n = 475). At week 24, the placebo-corrected adjusted mean (±se) change from baseline in HbA1c with linagliptin was -7 (±1) mmol/mol [-0.7 (±0.1) %; 95% CI -0.8, -0.6; P < 0.0001]. The overall frequency of drug-related adverse events (linagliptin, 18.9%; placebo, 21.9%) and investigator-reported hypoglycaemia (linagliptin, 30.7%; placebo, 31.6%) were similar in both groups at the end of treatment. The frequency of severe hypoglycaemia was low (linagliptin, 1.7%; placebo, 0.8%). No meaningful changes in mean (±sd) body weight were noted in either group [week 52: linagliptin, -0.5 (±3.2) kg; placebo, 0.0 (±3.1) kg]. CONCLUSIONS: Linagliptin added to basal insulin and metformin improved glycaemic control, without increasing the risk of hypoglycaemia or body weight gain.

Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data.

AIMS: To assess the long-term efficacy and tolerability of dapagliflozin versus glipizide as add-on to metformin in patients with inadequately controlled type 2 diabetes. METHODS: The present study was an extension of an earlier randomized, double-blind, phase III study of dapagliflozin (n = 406) vs glipizide (n = 408) to 208 weeks (4 years). Patients continued to receive their assigned medication. No statistical treatment-group comparisons were calculated. RESULTS: At 208 weeks, dapagliflozin compared with glipizide produced sustained reductions in glycated haemoglogin (HbA1c): -0.30% [95% confidence interval (CI), -0.51 to -0.09], in total body weight: -4.38 kg (95% CI -5.31 to -3.46) and in systolic blood pressure (SBP): -3.67 mmHg (95% CI -5.92 to -1.41). The HbA1c coefficient of failure was significantly lower for dapagliflozin than for glipizide: 0.19 (95% CI 0.12-0.25) versus 0.61 (95% CI 0.49-0.72, difference -0.42; p = 0.0001). Dapagliflozin was not associated with glomerular function deterioration, while this occurred more frequently in patients in the glipizide group. Fewer patients reported hypoglycaemia in the dapagliflozin compared with the glipizide group (5.4 vs 51.5%). Genital and urinary tract infections were more common with dapagliflozin than with glipizide, but their incidence decreased with time and all events responded well to antimicrobial treatment. CONCLUSIONS: In patients completing 4 years of treatment, dapagliflozin was well tolerated and associated with sustained glycaemic efficacy and greater reductions in body weight and SBP versus glipizide.

Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION).

AIMS: To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control. METHODS: In this multinational, randomized, double-blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged ≥65 years were randomized (1 : 1) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day, added to metformin, during a 52-week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) <7.0% at week 52 without confirmed/severe hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe hypoglycaemia. Safety and tolerability were also assessed. RESULTS: Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence interval 0.73, 1.34; p = 0.9415); however, a significant treatment-by-age interaction effect was detected (p = 0.0389): saxagliptin was numerically (but not significantly) superior to glimepiride for patients aged <75 years (39.2 vs 33.3%) and numerically inferior for patients aged ≥75 years (35.9 vs 45.5%). The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal p < 0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride. CONCLUSION: As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with T2D aged ≥65 years.

Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin.

AIMS: To assess the long-term glycaemic durability, safety and tolerability of dapagliflozin versus glipizide as add-on therapies in patients with type 2 diabetes inadequately controlled by metformin alone. METHODS: This was a 52-week, randomised, double-blind study of dapagliflozin (n = 406) versus glipizide (n = 408), uptitrated over 18 weeks according to tolerability and glycaemic response to a maximum of 10 and 20 mg/day, respectively, as add-on therapies to metformin (≥ 1500 mg/day) with a 156-week double-blind extension period. Data over 104 weeks are reported here. RESULTS: In total, 53.1% of patients completed 104 weeks of treatment. After the greater initial decrease (0-18 weeks) in glycated haemoglobin (HbA1c) with glipizide, the 18-104-week HbA1c coefficient of failure (CoF) was lower with dapagliflozin (0.13%/year) than with glipizide (0.59%/year), resulting in significant dapagliflozin versus glipizide differences of -0.46%/year (95% CI -0.60,-0.33; p = 0.0001) for CoF and -0.18%(-2.0 mmol/mol) [95% CI -0.33(-3.6),-0.03(-0.3); p = 0.021] for 104-week HbA1c. Dapagliflozin produced sustained reductions in weight and systolic blood pressure, whereas glipizide increased weight and systolic blood pressure, giving 104-week dapagliflozin versus glipizide differences of -5.1 kg (95% CI: -5.7,-4.4) and -3.9 mmHg (95% CI: -6.1,-1.7), respectively. Over 104 weeks, the hypoglycaemia rate was 10-fold lower with dapagliflozin than with glipizide (4.2 vs. 45.8%), whereas patient proportions with events suggestive of genital infection and of urinary tract infection (UTI) were greater with dapagliflozin (14.8 and 13.5%, respectively) than with glipizide (2.9 and 9.1%, respectively). CONCLUSIONS: Over 2 years, compared with glipizide, dapagliflozin demonstrated greater glycaemic durability, sustained reductions in weight and systolic blood pressure and a low hypoglycaemia rate; however, genital infections and UTIs occurred more frequently.

[Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin]. / Vergleich von Dapagliflozin und Glipizid als Add-on-Therapie bei Typ-2-Diabetikern mit unzureichender Blutzuckerkontrolle unter Metformin.

OBJECTIVE: Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS: This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA1c, 7.7 %), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤ 10 or ≤ 20 mg/day, respectively. RESULTS: The primary end point, adjusted mean HbA1c reduction with dapagliflozin (-0.52 %) compared with glipizide (-0.52 %), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (-3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥ 5 % body weight reduction (33.3 %) versus glipizide (2.5 %; p < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5 %) versus glipizide (40.8 %; p < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. CONCLUSIONS: Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.

Pioglitazona. Revisión de sus efectos metabólicos y sistémicos / Pioglitazone. Review of its metabolic and systemic effects

La diabetes mellitus tipo 2 se ha convertido en una verdadera epidemia y se espera un crecimiento importante en las próximas décadas. Se podría esperar, por tanto, que el impacto que ello puede tener sobre la incidencia y prevalencia de morbimortalidad cardiovascular sea de magnitudes considerables. El control metabólico (glucémico y lipídico) adecuado de los pacientes que la padecen, comenzando con programas de dieta y ejercicio y posteriormente con medidas farmacológicas, ha demostrado disminuir el riesgo de complicaciones. No obstante, diversos estudios han evidenciado que, independientemente del tratamiento utilizado, el control metabólico empeora con el tiempo. En los últimos años se ha incorporado una nueva familia de fármacos al arsenal terapéutico para tratar la diabetes mellitus tipo 2, las tiazolidinodionas o glitazonas, que aportan aspectos diferenciales respecto a otros fármacos. En este artículo se revisan los efectos metabólicos y sistémicos de pioglitazona, que recientemente ha demostrado en el estudio PROactive un efecto positivo en la prevención secundaria de episodios cardiovasculares

Type 2 diabetes mellitus has become a true epidemic and significant growth is expected in the next decades. Thus it could be expected that the impact it may have on the incidence and prevalence of cardiovascular morbidity-mortality will have considerable magnitudes. It has been demonstrated that adequate metabolic control (glycemic and lipid) of these patients, beginning with diet and exercise programs and then with drug measures, decreases the risk of complications. However, several studies have shown that metabolic control deteriorates over time regardless of the treatment used. In recent years, a new drug family has been incorporated into the therapeutic armamentarium to treat type 2 diabetes mellitus. These are thiazolidinediones or glitazones, which have differential aspects regarding other drugs. In this article, the metabolic and systemic effects of pioglitazone, that have recently demonstrated a positive effect in the secondary prevention of cardiovascular episodes in the PROactive study have been reviewed

[Pioglitazone. Review of its metabolic and systemic effects]. / Pioglitazona. Revisión de sus efectos metabólicos y sistémicos.

Type 2 diabetes mellitus has become a true epidemic and significant growth is expected in the next decades. Thus it could be expected that the impact it may have on the incidence and prevalence of cardiovascular morbidity-mortality will have considerable magnitudes. It has been demonstrated that adequate metabolic control (glycemic and lipid) of these patients, beginning with diet and exercise programs and then with drug measures, decreases the risk of complications. However, several studies have shown that metabolic control deteriorates over time regardless of the treatment used. In recent years, a new drug family has been incorporated into the therapeutic armamentarium to treat type 2 diabetes mellitus. These are thiazolidinediones or glitazones, which have differential aspects regarding other drugs. In this article, the metabolic and systemic effects of pioglitazone, that have recently demonstrated a positive effect in the secondary prevention of cardiovascular episodes in the PROactive study have been reviewed.

[A glucose tolerance study in the 12 months postpartum in patients with gestational diabetes]. / Estudio de la tolerancia a la glucosa en los 12 meses posparto en pacientes con diabetes gestacional.

BACKGROUND: It has been reported that patients with gestational diabetes have a considerable long term risk of developing diabetes mellitus. METHOD: Glucose tolerance was studied in the 12 months following birth in 155 patients diagnosed by the authors as having gestational diabetes and followed during pregnancy. RESULTS: It was observed that in 48% of the patients alterations persisted (33% glucose intolerance and 15% diabetes mellitus). Glucose tolerance during gestation and the perinatal results were retrospectively analyzed with a relation with the postpartum reclassification being observed. CONCLUSIONS: It was estimated that the percentage of alterations in glucose tolerance persisting postpartum is extremely high, suggesting the need for this test with a double objective: the reclassification of gestational diabetes and the early detection of glucose intolerance and diabetes mellitus.

[The dawn phenomenon in diabetic pregnancy]. / Estudio del fenómeno del alba en la embarazada diabética.

The possible development of the dawn phenomenon in three gestational stages was investigated in 9 pregnant women with type I diabetes mellitus and 10 with gestational diabetes. To this end, the overnight intravenous insulin infusion was evaluated with the artificial pancreas (Biostator). In none of the two clinical conditions and in none of the three gestational stages an increased insulin infusions during the second period of the night was found under the experimental conditions of our study. This finding may we related with the timing of the last food intake.

[Evaluation of diabetes knowledge in patients with insulin-dependent diabetes mellitus. Influential factors and analysis of its relation with blood glucose control]. / Evaluación del nivel de conocimientos diabetológicos en pacientes con diabetes mellitus insulinodependientes. Factores influyentes y análisis de la relación con el control glucémico.

The level of diabetes education has been evaluated by means of a test questionnaire with 62 items in a group of 57 insulin-dependent Diabetes Mellitus (type I) patients who were cared for at a Hospital Diabetes Unit for a least six months prior the study. We observed that only 60% of our patients had an acceptable diabetes education. Our educational programme seems to be efficient for patients between 20 and 40 years old with a High School or University degree, although we think that the educational method should be changed for older or less educated patients. Moreover, we have analyzed the possible influence of diabetes education on the glycemic control, both globally, and in specific areas. We observed a significantly lower MBG in the patient group with a higher level of diabetes knowledge. The MBG and HbA1c values correlate with training in blood glucose autoanalysis.

[Evaluation of the insulin requirements with an artificial pancreas in the pregnant woman with gestational insulin-dependent diabetes (type I)]. / Valoración de los requerimientos insulínicos con páncreas artificial en la embarazada con diabetes pregestacional insulinodependiente (tipo I).

The evolution of insulin requirements in 9 pregnant women with insulin-dependent diabetes mellitus (type I) was evaluated. Requirements were increased between weeks 11 and 24 and remained stable between weeks 24 and 35. Those corresponding to breakfast in the two initial connections were significantly higher, while those corresponding to breakfast, lunch and dinner became equal in the last connection (35 gestational weeks). We found a significant lineal correlation between the intravenous and the subcutaneous requirements. We conclude that the artificial pancreas is a useful instrument, which permits a detailed analysis of the time course of intravenous insulin requirements during pregnancy in the insulin-dependent pregnant woman and facilitates the adjustment of insulin therapy.

[Evaluation of the insulin requirements with an artificial pancreas in gestational diabetes]. / Valoración de los requerimientos insulínicos con páncreas artificial en la diabetes gestacional.

The evolution of insulin requirements in 10 patients with gestational diabetes mellitus was evaluated with the use of an artificial pancreas. We found that intravenous insulin requirements showed a definite tendency to decline, the greatest reduction being found between gestational weeks 27 and 37. Postprandial requirements after lunch were significantly higher in the weeks 15 and 27, with a tendency to become equal to those corresponding to breakfast and dinner in week 37. We found a lack of lineal correlation between the intravenous and subcutaneous requirements. We conclude that the artificial pancreas is a useful instrument to examine in detail the temporal evolution of insulin requirements in gestational diabetes. The artificial pancreas facilitates the adjustment of insulin therapy and plays a major role in the understanding of the pathophysiological abnormalities in these patients.