Efficacy and safety of an expanded dulaglutide dose range: A phase 2, placebo-controlled trial in patients with type 2 diabetes using metformin.

AIMS: Dulaglutide, a once weekly GLP-1 receptor agonist, is approved at two doses (1.5 and 0.75 mg) for treatment of type 2 diabetes (T2D). Two higher doses of dulaglutide (3.0 and 4.5 mg) were evaluated for safety and efficacy to determine whether these doses warrant further study for improved control of glucose and body weight. MATERIALS AND METHODS: This 18-week, double-blind, phase 2 trial randomized 318 patients with T2D using ≥1500 mg metformin, to receive subcutaneous injection of placebo (n = 82), dulaglutide 1.5 mg (n = 81), dulaglutide 3.0 mg (n = 79) or dulaglutide 4.5 mg (n = 76). The primary objective was superiority of dulaglutide doses over placebo in reduction of HbA1c at 18 weeks. Secondary objectives included superiority of dulaglutide over placebo in change from baseline in body weight and fasting serum glucose (FSG) at 18 weeks. Investigational doses of dulaglutide were compared to the 1.5 mg dose as an exploratory objective. RESULTS: HbA1c reduction at 18 weeks was significantly greater with dulaglutide vs placebo (placebo, -0.44% ± 0.10% [-4.8 ± 1.1 mmol/mol]; dulaglutide 1.5 mg, -1.23% ± 0.10% [-13.5 ± 1.1 mmol/mol]; dulaglutide 3.0 mg, -1.31% ± 0.10% [-14.3 ± 1.1 mmol/mol]; dulaglutide 4.5 mg, -1.40% ± 0.10% [-15.3 ± 1.1 mmol/mol]; P < 0.001, each dose), as were changes in body weight (placebo, -1.6 ± 0.39 kg; dulaglutide 1.5 mg, -2.8 ± 0.39 kg; dulaglutide 3.0 mg, -3.9 ± 0.39 kg; dulaglutide 4.5 mg, -4.1 ± 0.41 kg; P < 0.001, each dose). All three dulaglutide doses significantly reduced FSG from baseline (1.5 mg, -36.2 ± 4.7 mg/dL [-2.0 ± 0.3 mmol/L]; 3.0 mg, -34.5 ± 4.5 mg/dL [-1.9 ± 0.3 mmol/L]; 4.5 mg, -38.0 ± 4.7 mg/dL [-2.1 ± 0.3 mmol/L]) vs placebo (-12.4 ± 4.5 mg/dL [-0.7 ± 0.3 mmol/L]) (P < 0.001, all). Safety profiles of the higher doses were consistent with the established safety profile for dulaglutide. Gastrointestinal events were mostly mild to moderate, and was dose-related for nausea. CONCLUSION: All three dulaglutide doses were superior to placebo in improving glycaemic control and reducing body weight in participants with T2D using metformin. The potential for doses of dulaglutide of 3.0 and 4.5 mg to provide additional glycaemic benefit and weight reduction with an acceptable safety profile, compared with the 1.5 mg dose, warrants further study in a phase 3 trial.

Diabetes in pregnancy: current ways of treatment.

It is well known, that number of diabetics pregnancies is raising. It is due to growing amount of women with type 1 and type 2 diabetes, which can easily reach the right age for pregnancy. It allows new ways of diabetes treatment, new technologies and in general better health state of this women. Displacement the pregnancy to later age, leads to gestational diabetes increasing. Especially women with pregestational diabetes are in higher risk of perinatal and diabetic complications. More than half of all pregnancies are not planned and so that often not well controlled or used inappropriate medication. Preterm deliveries, acute sectiones cesarea, eclampsia, preeclampsia or higher risk of late diabetics complications are in consequencies. The article brings the current point of view to treatment diabetic pregnancies with respect to prevent all types of complications.

Maternal BMI and HDL as predictors of pregnancy outcome in women with type 1 diabetes.

OBJECTIVE: Diabetes in pregnancy is associated with increased risks of maternal as well as foetal complications. METHODS: Retrospective data on 96 women and their 96 newborns were anonymously statistically analysed to assess pregnancies of type 1 diabetes (T1D) women managed in our hospital in past nine years. The outcomes of the neonates were divided into three categories according to the clinical status, presence of congenital abnormalities and infant's treatment. RESULTS: We found out that the outcome of newborn infants associated with maternal HbA1c before gestation as well as during the whole course of pregnancy (p < 0.02 for all). Surprisingly, neonatal outcome was strongly associated with the maternal BMI (p < 0.05). In our model, a lowering of BMI by one grade led to an 18% increase in the chance that the newborn will have no health problems. We did not observe an important worsening of chronic diabetic complications in mothers; however, regarding maternal clinical status, we found that preeclampsia occurrence was strongly and independently connected to HDL level (p < 0.01). CONCLUSION: Our data demonstrate that lower pregestational BMI could substantially improve T1D mothers' pregnancy outcome. Lower HDL levels in T1D mothers during pregnancy correlate with higher risk of preeclampsia development.

Experience with real time continuous glucose monitoring in stabilising fluctuating glycaemia during intensive care of the preterm infant of a diabetic mother.

OBJECTIVE: The newborns of diabetic mothers suffer from perinatal complications more frequently than the newborns of healthy women. METHODS: We used for 7 days a real time continuous glucose monitoring system (RT-CGMS) to monitor glucose homeostasis and manage glucose administration in a premature newborn of a diabetic mother. RESULTS: The boy was born at 35 + 5 gestational weeks with typical signs of diabetic fetopathy. RT-CGMS revealed 2 late hypoglycaemia episodes on the 2nd and 4th days. The sensor readings correlated well with glycaemia measured in the laboratory (r = 0.908, p = 0.005). To support conclusions of this case report, we attached the data of five other preterm newborns of diabetic mothers who were later successfully treated according to the RT-CGMS data as well. CONCLUSIONS: This approach allows timely response to glycaemia instability and is applicable even in preterm infants.

Impact of self-measurement of blood glucose on complications of type 2 diabetes: economic analysis from a Czech perspective.

OBJECTIVE: A growing body of evidence indicates that self-measurement of blood glucose (SMBG) also has beneficial effects in people with type 2 diabetes, irrespective of the type of therapy. The objective of this analysis was to determine the economic impact of SMBG by comparing the cost share of self-monitoring and the direct costs of diabetes-related complications in users and non-users. RESEARCH DESIGN AND METHODS: A matched-pair analysis based on the cohorts of a large retrospective study of patients with type 2 diabetes (ROSSO) was conducted. The average annual direct costs of diabetes monitoring, treatment-related services, complications and follow-up costs of the disease for SMBG users versus non-users were calculated from the perspective of the Czech statutory health insurance system. Univariate sensitivity analysis was performed to determine the main cost drivers. Limitations of this study are: (1) differences in medical facilities/practice between Germany and the Czech Republic, (2) causal relationship between SMBG and health outcomes is missing, (3) ROSSO underestimated the number of test strips used, (4) Czech cost data are scarce. RESULTS: In patients treated with oral antidiabetic drugs (OAD) only, total annual costs in Czech koruna (CZK) were CZK 16 476 for SMBG users and CZK 19 440 for non-users. In patients treated with OAD + insulin, total annual costs were CZK 32 590 and CZK 48 600, respectively. The main cost drivers were stroke and myocardial infarction in patients treated with OAD only, and stroke, dialysis and myocardial infarction in patients treated with OAD + insulin. CONCLUSION: Cost analysis indicated that SMBG provides a rapid return on initial investment. By increasing the number of patients using SMBG, the statutory health insurance system in the Czech Republic may save several million CZK annually.

Improved glycemic control through continuous glucose sensor-augmented insulin pump therapy: prospective results from a community and academic practice patient registry.

BACKGROUND: Conducted by highly experienced investigators with abundant time and resources, phase III studies of continuous glucose sensing (CGS) may lack generalizability to everyday clinical practice. METHOD: Community or academic practices in six Central and Eastern European or Mediterranean countries prospectively established an anonymized registry of consecutive patients with type 1 insulin-dependent diabetes mellitus starting CGS-augmented insulin pump therapy with the Paradigm X22 (Medtronic MiniMed, Northridge, CA) under everyday conditions, without prior CGS with another device. We compared glycosylated hemoglobin (GHb) values before and after 3 months of CGS and assessed relationships between insulin therapy variables and glycemia-related variables at weeks 1, 4, and 12 of CGS. RESULTS: Of 102 enrolled patients, 85 (83%) with complete weeks 1, 4, and 12 sensor data and baseline/3-month GHb data were evaluable. Evaluable patients were approximately 54% male and approximately 75% adult (mean age, 33.2 +/- 16.9 years) with longstanding diabetes and high personal/family education levels. Mean GHb declined significantly after 3 months of CGS (7.55 +/- 1.33% at baseline to 6.81 +/- 1.08% after 12 weeks, 0.74% absolute decrease, P < 0.001). The absolute GHb reduction correlated significantly (P < 0.0005) with baseline GHb: larger absolute reductions tended to occur when baseline levels were higher. An increased basal insulin dose as a percentage of the total daily insulin dose and a decreased daily bolus count from week 1 to week 12 of CGS predicted GHb improvement from baseline to week 12. CONCLUSIONS: CGS-augmented insulin pump therapy appears to improve glycemic control in type 1 diabetes in varied everyday practice settings.