Background: No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap. Methods: Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events. Results: From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, –0.58%; 95% confidence interval, –0.75 to –0.40; P<0.00001; I2=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG). Conclusion Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.

Background: 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. Methods: 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. Results: 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). Conclusion Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.

Background: 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. Methods: 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. Results: 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). Conclusion Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.

Background: No meta-analysis has analysed efficacy and safety of fast-acting aspart insulin (FIAsp) with insulin pump in type 1 diabetes mellitus (T1DM). Methods: 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. Results: 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. Conclusion FIAsp use in insulin pump is associated with better post-prandial glycaemic control with no increased hypoglycaemia or glycaemic variability.

Purpose: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap. Methods: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events. Results: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93–3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08–2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01–8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44–12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21–96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24–26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, β-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05–0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001). Conclusion SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.

Purpose: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap. Methods: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events. Results: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93–3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08–2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01–8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44–12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21–96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24–26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, β-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05–0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001). Conclusion SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.

Purpose: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap. Methods: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events. Results: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93–3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08–2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01–8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44–12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21–96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24–26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, β-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05–0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001). Conclusion SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.

PURPOSE: The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status.METHODS: Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis.RESULTS: Partial response (PR), stable disease (SD) and progressive disease (PD) for PSAwere seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88 GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables.CONCLUSION: We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.
Creatinine ; Humans ; Leukocyte Count ; Leukopenia ; Lutetium ; Membranes ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Thrombocytopenia

PURPOSE: The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status. METHODS: Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis. RESULTS: Partial response (PR), stable disease (SD) and progressive disease (PD) for PSAwere seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88 GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables. CONCLUSION We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.

A 62-year-female presented with bilateral proptosis and 1 year episodic eye pain, grittiness, redness, watering and intermittent diplopia for 6 months, and drooping of right eye lid for 2 months (Figure 1). She had a firm WHO grade-1b goiter, exopthalmos (26 mm and 23 mm in left and right eye respectively, Hertel exopthalmometer), clinical activity score of 1/6, without any evidence of bulbar, neck muscles and limb weakness.
Graves Ophthalmopathy ; Hypothyroidism