Scant data is available on the efficacy and safety of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) for early and rapid reduction of low-density lipoprotein cholesterol (LDL-C) ...within 4–8 weeks of an acute event in patients with acute coronary syndrome (ACS). We undertook this meta-analysis to address this knowledge-gap.
Electronic databases were searched for RCTs involving patients with ACS receiving PCSK9i in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in 1-month LDL-C post ACS. Secondary outcomes were to evaluate alterations in other lipid parameters and adverse events.
From initially screened 194 articles, data from 3 studies was analyzed. After 4-weeks therapy, patients receiving PCSK9i had lower LDL-C MD -0.95 mmol/L (95%CI:-1.51 to −0.40); P = 0.0007; I2 = 96%, total cholesterol (TC) MD-1.05 mmol/L (95%CI:-1.83 to −0.27); P = 0.009; I2 = 94% and triglycerides (TG) MD-0.27 mmol/L (95%CI:-0.44 to −0.10); P = 0.002; I2 = 0% compared to controls. After 4–8 weeks therapy, patients receiving PCSK9i has lower apolipoprotein B MD-27.74% (95%CI:-42.59 to −12.89); P = 0.0003; I2 = 89% as compared to controls. High density lipoprotein cholesterol (HDL-C) MD 0.05 mmol/L (95%CI:-0.00–0.11); P = 0.05; I2 = 0%, lipoprotein(a) MD-20.63 mmol/L (95%CI:-41.86– 0.59); P = 0.06; I2 = 54% and apolipoprotein A1 MD 0.02 g/L (95%CI:-0.02–0.07); P = 0.32; I2 = 0% were comparable between groups. Hospital readmission for ACS was significantly lower in group receiving PCSK9i compared to controls OR0.25 (95%CI:0.07–0.85); P = 0.03; I2 = 0%. Occurrence of cardiac death OR3.75 (95%CI:0.41–34.22); P = 0.24; I2 = 0%, serious adverse events OR0.71 (95% CI:0.13–3.83); P = 0.69; I2 = 70% and total adverse events OR1.01 (95%CI: 0.19–5.30); P = 0.99; I2 = 92% was comparable between groups.
PCSK9i are highly effective in early reduction of LDL-C along with reduction of early hospital readmissions post-ACS.
No meta-analysis has analysed efficacy and safety of fast-acting aspart insulin (FIAsp) with insulin pump in type 1 diabetes mellitus (T1DM).
Electronic databases were searched for randomised ...controlled trials (RCTs) involving T1DM patients on insulin pump receiving FIAsp in intervention arm, and placebo/active comparator insulin in control arm. Primary outcome was to evaluate changes in 1- and 2-hour post-prandial glucose (1hPPG and 2hPPG). Secondary outcomes were to evaluate alterations in percentage time with blood glucose <3.9 mmol/L (hypoglycaemia), time in range (TIR) blood glucose 3.9 to 10 mmol/L, insulin requirements and adverse events.
Data from four RCTs involving 640 patients was analysed. FIAsp use in insulin pump was associated with significantly greater lowering of 1hPPG (mean difference MD, -1.35 mmol/L; 95% confidence interval CI, -1.72 to -0.98; P<0.01; I2=63%) and 2hPPG (MD, -1.19 mmol/L; 95% CI, -1.38 to -1.00; P<0.01; I2=0%) as compared to controls. TIR was comparable among groups (MD, 1.06%; 95% CI, -3.84 to 5.96; P=0.67; I2=70%). Duration of blood glucose <3.9 mmol/L was lower in FIAsp group, approaching significance (MD, -0.91%; 95% CI, -1.84 to 0.03; P=0.06; I2=0%). Total hypoglycaemic episodes (risk ratio RR, 1.35; 95% CI, 0.55 to 3.31; P=0.51; I2=0%), severe hypoglycaemia (RR, 2.26; 95% CI, 0.77 to 6.66; P=0.14), infusion site reactions (RR, 1.35; 95% CI, 0.63 to 2.93; P=0.77; I2=0%), and treatment-emergent adverse events (RR, 1.13; 95% CI, 0.80 to 1.60; P=0.50; I2=0%) were comparable.
FIAsp use in insulin pump is associated with better post-prandial glycaemic control with no increased hypoglycaemia or glycaemic variability.
No meta-analysis is available which has analysed the role of letrozole in constitutional delay in growth and puberty (CDGP). Electronic databases were searched for randomized controlled trials (RCTs) ...involving children with CDGP receiving letrozole. Primary outcomes were changes in predicted adult height (PAH) and pubertal progression. Secondary outcomes were alterations in bone age (BA), hormonal markers of puberty, bone mineral density and side-effects. One hundred-thirty articles were reviewed, from which seven RCTs which fulfilled all criteria were analysed. Letrozole was superior to placebo mean difference (MD) 4.63 cm (95% confidence interval (CI): 3.90-5.36); p<0.01; I
=0% but not testosterone MD: 2.21 cm (95% CI: -1.71-6.16); p=0.27; I
=98% with regards to improvement in PAH after 12-months use. Letrozole was superior to both placebo MD: 4.80 mL (95% CI: 0.57-9.03); p=0.03 and testosterone MD: 3.36 mL (95% CI: 0.58-6.75); p=0.02; I
=0% with regards to improvement in testicular volume after 12-months use. Letrozole tended to be superior to testosterone MD: -0.84 years (95% CI: 2.83-8.18); p=0.06; I
=0% with regards to slowing in BA progression after 12-months use. Serum luteinizing hormone, follicle stimulating hormone, testosterone and inhibin-B were significantly higher after 6-months letrozole use compared to active as well as passive controls. No increased occurrence of adverse events, including spinal deformities, were noted with letrozole. Letrozole is safe and effective for improving height and pubertal outcomes in CDGP, and is better than testosterone with regards to improvement in testicular volume and may be better at delaying bone-age progression.
Endocrinology is relatively one of the newer super-specialties of internal medicine. Following higher secondary schooling, it takes anywhere between 13 and 18 years to become a super-specialist in ...India, which holds true for endocrinology also. This article intends to highlight the life and the journey of making an endocrinologist in India, through personal experiences, focusing on Institute of Post Graduate Medical Education and Research (IPGMER) Calcutta, the largest super-specialty teaching hospital and research institute of Eastern India. In general, there is lack of adequate exposure to endocrinology during the Bachelor of Medicine, Bachelor of Surgery and MD Internal Medicine Training in India. Pre-Doctorate of Medicine (DM) senior residency goes a long way in developing an orientation for endocrinology. Endocrinology DM entrance examinations are usually a rigorous intimidating affair. Endocrinology training at IPGMER was a heady mix of managing huge number of patients with diverse endocrinopathies, laboratory work, academic presentations, and clinical research. The support and back up provided by the entire faculty enhanced the learning process. As I look back, the 3 years of DM residency flew by like the wink of the eye. The journey of endocrinology is the journey of a lifetime.
Sleep Disorders in Type 2 Diabetes Khandelwal, Deepak; Dutta, Deep; Chittawar, Sachin ...
Indian journal of endocrinology and metabolism,
09/2017, Letnik:
21, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Type 2 diabetes mellitus (T2DM) has shown to be associated with higher incidence of sleep disorders, which may be due to disease itself or because of secondary complications or associated ...comorbidities associated with diabetes. On the other hand, shorter sleep duration and erratic sleep behavior itself have been linked with higher incidence of obesity, metabolic syndrome, and T2DM. Assessment of sleep quality and sleep disorders as a part of the comprehensive medical evaluation is recommended based on emerging evidence suggesting a relationship between sleep quality and glycemic control in persons with T2DM. In this review, we attempt to summarize common sleep disorders associated with T2DM, their impacts on glycemic and other metabolic control, and various preventive and therapeutic strategies to tackle these problems.
Background: Mechanistically, subcutaneous ultra-rapid lispro (URLi) is faster than lispro. Whether this translates into a better post-prandial glucose (PPG) and glycemic control in type-1 diabetes ...(T1DM) and type-2 diabetes (T2DM) is unclear. Hence, we undertook this meta-analysis. Methods: Databases were searched for randomized controlled trials (RCTs) involving patients with T1DM/T2DM receiving URLi in intervention-arm, and placebo/prandial insulin as control. The primary outcome was a change in PPG. Secondary outcomes were alterations in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), time in range (TIR), and adverse events. Results: Data from six RCTs (3687 patients) were analyzed. Lispro was the control arm in all RCTs. T1DM patients receiving mealtime URLi had lower HbA1c mean difference (MD) −0.07%; 95% confidence interval (CI): −0.12 to − 0.01; P = 0.02; I2 = 42% and 1-h PPG MD − 1.18 mmol/L; 95% CI: −1.91 to − 0.44; P = 0.002; I2 = 100%. T1DM patients receiving post-meal URLi had comparable HbA1c MD 0.07%; 95% CI: −0.01 to 0.15; P = 0.07; I2 = 55% and 1-h PPG MD 0.22 mmol/L; 95% CI: −0.80 to 1.24; P = 0.67; I2 = 100%). T1DM patients on pumps receiving URLi had comparable TIR MD 1.70; 95% CI: −0.29 to 3.69; P = 0.09; I2 = 98%, lower time in blood glucose <3 mmol/L with increased infusion-set reactions. T2DM patients receiving mealtime URLi had lower 1-h PPG MD − 0.66 mmol/L; 95% CI: −0.69 to − 0.63; P < 0.00001; I2 = 0%(LH), 2-h-PPG MD − 0.96 mmol/L; 95% CI: −1.00 to − 0.92; P < 0.00001; I2 = 0%, higher FPG MD 0.18 mmol/L; 95% CI: 0.11–0.24; P < 0.00001; I2 = 20%, and higher HbA1c MD 0.07%; 95% CI: −0.06 to 0.08; P < 0.00001; I2 = 0%. Conclusion: Pre-meal URLi is better than lispro with regard to PPG control. Post-meal URLi is as good as lispro for PPG control. Post-meal URLi is inferior to pre-meal URLi for PPG control.
No meta-analysis has holistically analysed and summarised the efficacy and safety of gemigliptin in type 2 diabetes. The meta-analysis addresses this knowledge gap.
Electronic databases were searched ...for randomised controlled trials (RCTs) involving diabetes patients receiving gemigliptin in the intervention arm and placebo/active comparator in the control arm. The primary outcome was change in haemoglobin A1c (HbA1c). The secondary outcomes were alterations in glucose, glycaemic targets, lipids, insulin resistance, and adverse events.
Data from 10 RCTs involving 1,792 patients were analysed. Four had an active control group (ACG), with metformin/dapagliflozin/sitagliptin/glimepiride as the active comparator; six had a passive control group (PCG), with placebo/rosuvastatin as controls. HbA1c reduction by gemigliptin at 24 weeks was comparable to ACG (mean difference MD, 0.09%; 95% confidence interval CI, -0.06 to 0.23; P=0.24; I2=0%; moderate certainty of evidence MCE), but superior to PCG (MD, -0.91%; 95% CI, -1.18 to -0.63); P<0.01; I2=89%; high certainty of evidence HCE). Gemigliptin was superior to PCG regarding achieving HbA1c <7% (12 weeks: odds ratio OR, 5.91; 95% CI, 1.34 to 26.08; P=0.02; I2=74%; 24 weeks: OR, 4.48; 95% CI, 2.09 to 9.60; P<0.01; I2=69%; HCE). Gemigliptin was comparable to ACG regarding achieving HbA1c <7% after 24 weeks (OR, 0.92; 95% CI, 0.52 to 1.63; P=0.77; I2=66%; MCE). Adverse events were similar between the gemigliptin and control groups (risk ratio RR, 1.06; 95% CI, 0.82 to 1.36; P=0.66; I2=35%; HCE). The gemigliptin group did not have increased hypoglycaemia (RR, 1.19; 95% CI, 0.62 to 2.28; P=0.61; I2=19%; HCE).
Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.
Background: Till date, there is no Cochrane meta-analysis available which has analyzed efficacy and safety of tirzepatide in type-2 diabetes. This meta-analysis was undertaken to address this ...knowledge gap. Methods: Electronic databases were searched for randomized controlled trials (RCTs) involving people with diabetes receiving tirzepatide compared to a placebo/active comparator. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood-glucose, glycemic targets, weight, lipids, and adverse events. Results: From 34 articles initially screened, data from six RCTs involving 3484 patients were analyzed. Over 12-52 weeks, individuals receiving tirzepatide had significantly greater lowering of HbA1c mean difference (MD) = -0.75% (95% confidence interval (CI): -1.05 to -0.45); P < 0.01; I2 = 100%, fasting glucose MD = -0.75 mmol/L (95% CI: -1.05 to- -0.45); P < 0.01; I 2 = 100%, 2-h post-prandial-glucose MD = -0.87 mmol/L (95% CI: -1.12 to -0.61); P < 0.01; I2 = 99%, weight MD = -8.63 kg (95% CI: -12.89 to -4.36); P < 0.01; I2 = 100%, body mass index MD = -1.80 kg/m2 (95% CI: -2.39 to -1.21); P < 0.01; I2 = 99%, and waist circumference MD = -4.43 cm (95% CI: -5.31 to -3.55); P < 0.01; I2 = 95% as compared to dulaglutide, semaglutide, degludec, or glargine. Patients receiving tirzepatide had higher odds of achieving HbA1c <6.5% compared to active controls odds ratio (OR) = 4.39 (95% CI: 2.44-7.92); P < 0.01; I2 = 90%. Tirzepatide use had significantly higher odds of weight loss >5% OR = 19.18 (95% CI: 2.34-157.17); P < 0.01; I2 = 99%, >10% OR = 21.40 (95% CI: 2.36-193.94); P < 0.01; I2 = 98%, and >15% OR = 32.84 (95% CI: 2.27-474.33); P = 0.01; I2 = 96% compared to active-control group. Treatment-emergent adverse events risk ratio (RR) = 1.43 (95% CI: 1.14-1.80); P < 0.01; I2 = 40% and severe adverse events RR = 1.00 (95% CI: 0.64-1.57); P = 1.00; I2 = 49% were not different. High data heterogeneity and the presence of publication bias limits the grading of current data from "moderate to low." Conclusion: Tirzepatide has impressive glycemic efficacy and weight-loss data over 1-year clinical use. The need for higher grade, long-term efficacy, and safety data remains.
No meta-analysis is available which has analysed the role of aromatase inhibitors (AIs) in hypogonadism in adult males related to obesity and aging. This meta-analysis intended to address this ...knowledge gap. Electronic databases were searched for studies involving adult males with hypogonadism. The primary outcomes were changes in total testosterone (TT). Secondary outcomes were alterations in oestradiol, luteinizing hormone (LH), and side-effect profile. From initially screened 177 articles, data from three randomised controlled trials(RCTs) (118 patients) and three uncontrolled studies(52 patients) were analysed. AIs were associated with significantly greater improvement in TT after three months mean difference (MD) 7.08 nmol/L (95% Confidence Interval (CI): 5.92-8.24); P < 0.01; I2 = 0%, six months MD 6.61 nmol/L (95% CI: 5.30-7.93); P < 0.01 and 12 months MD 5.20 nmol/L (95% CI: 3.78-6.62); P < 0.01 therapy. AIs were associated with greater reduction in oestradiol after three months MD -3.07 pmol/L (95% CI: -5.27- -0.87); P < 0.01; I2 = 40%, six months MD -5.39 pmol/L (95% CI: -7.18- -3.60); P < 0.01 and 12 months MD -8.3 pmol/L (95% CI: -15.97- -0.63); P = 0.03 therapy. AIs were associated with greater increase in LH after three months MD 1.79 IU/L (95% CI: 0.77-2.81); P < 0.01; I2 = 0%, six months MD 2.20 IU/L (95% CI: 0.29 - 4.11); P = 0.02 and 12 months MD 1.70 IU/L (95% CI: 0.28-3.12); P = 0.02 therapy. Occurrence of treatment-emergent adverse eventsRisk ratio (RR) 1.48 (95% CI: 0.47-4.66); P = 0.45; I2 = 0% and severe adverse eventsRR 2.48 (95% CI: 0.42-14.66); P = 0.32; I2 = 0% were similar among AIs and controls. Following six-month treatment, AIs were associated with significantly lower bone mineral density (BMD) at lumbar-spine MD -0.04 gm/cm2 (95% CI: -0.08- -0.01); P = 0.03, but not total hip MD 0.01 gm/cm2 (95% CI: -0.02-0.04); P = 0.55 and femoral neck MD 0.02 gm/cm2 (95% CI: -0.01-0.05); P = 0.12 compared to controls. This meta-analysis highlights the good efficacy of AIs in improving TT over 3-12 months of use. Adverse impact on spine bone density remains a concern in obese ageing males and warrants further evaluation.
Saroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia.
Electronic ...databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) active control group (ACG) and those receiving placebo/diabetes medications passive control group (PCG).
Following 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG MD -71.67 mg/dl (95% CI: −123.67 to −19.66 mg/dl); P < 0.01; I2 = 91% (considerable heterogeneity); low certainty of evidence (LCE), but not ACG MD -37.38 mg/dl (95% CI: −84.55–9.79 mg/dl; P = 0.12; I2 = 98% (considerable heterogeneity); LCE. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG MD -24.61 mg/dl (95% CI: −44.13 to −5.09 mg/dl); P = 0.01; I2 = 65% (moderate heterogeneity); LCE, but not ACG MD -13.5 mg/dl (95% CI: −33.1–6.10 mg/dl; P = 0.18; I2 = 98% (considerable heterogeneity); LCE. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls MD 0.12 mg/dl (95% CI: 0.04–0.21 mg/dl); P < 0.01; I2 = 29% (low heterogeneity); high certainty of evidence.
This meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.
•Data from five studies (378 patients) was analysed to evaluate efficacy and safety of saroglitazar.•Saroglitazar has statistically significant triglyceride reduction when compared to passive but not active controls.•Saroglitazar has minimal impact on HBA1c, total cholesterol, LDL cholesterol, apolipoprotein-B and HDL cholesterol.•Serum creatinine was significantly higher in patients on saroglitazar, compared to controls +0.12 mg/dl.
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