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The article discusses the alpha-glucosidase inhibitors and thiazolidinediones that are older classes of oral type 2 diabetes medication. Topics discussed include acarbose that is an alpha-glucosidase inhibitor available in Australia, diagnosis of impaired glucose tolerance, and safety concerns which were raised about the use of rosiglitazone.

Abstract Background:: Few large randomized controlled trials have assessed the value of adding insulin to an oral antidiabetic drug regimen. Objective:: This trial compared the efficacy and safety of biphasic insulin aspart 30/70 (BIAsp 30) plus pioglitazone (n = 93), glibenclamide (glyburide) plus pioglitazone (n = 91), or BIAsp 30 monotherapy (n = 97). Methods:: This 18-week, multinational, multicenter, randomized, open-label, parallel-group trial involved 281 patients with type 2 diabetes (60% male; mean age, 56 years; mean body mass index, 29.5 kg/m2) with inadequate glycemic control (mean glycosylated hemoglobin [HbA1c], 9.5%; range, 7.4%–14.7%) on glibenclamide monotherapy or combination therapy. The primary objective was to compare end-of-trial HbA1c among the 3 treatment groups. Fasting and mean 7- and 8-point blood glucose profiles, blood lipid levels, plasminogen activator inhibitor levels, adverse events, and hypoglycemia frequency were also compared. Patients using BIAsp 30 (alone or with pioglitazone) were injected twice daily (immediately before breakfast and dinner). Pioglitazone (30 mg/d) and glibenclamide (5–15 mg/d) were taken orally once daily with or immediately after breakfast. Results:: At the end of the trial, HbA1c was significantly lower for the BIAsp 30 plus pioglitazone group than for the glibenclamide plus pioglitazone group (mean [SD], −0.64% [0.23%]; P = 0.005) and the BIAsp 30 monotherapy group (−0.60% [0.22%]; P = 0.008). Mean (SD) fasting blood glucose (before breakfast) was significantly lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone (153 [45] mg/dL vs 169 [65] mg/dL, respectively; P = 0.012). Each time point on the 8-point blood glucose profile was lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone (P < 0.001 to P < 0.05). No major hypoglycemic episodes were reported, and the absolute rate of hypoglycemic events was low (<1 event/patient-week) in the BIAsp-only group. Edema was reported in ≤9% of patients in each treatment group, but no occurrence was classified as serious. Weight gain (mean, 4.0 kg) was more common in the BIAsp plus pioglitazone group (8%); however, this was consistent with improved glycemic control and is similar to that reported in other pioglitazone trials. Conclusions:: BIAsp 30 plus pioglitazone provided an efficacious and well-tolerated treatment alternative to glibenclamide plus pioglitazone or BIAsp 30 alone in this population of patients who previously were not well controlled on glibenclamide monotherapy or combination therapy. [Copyright &y& Elsevier]

Issues Addressed Methods Results Conclusions So What? Addressing the disproportionate burden of type 2 diabetes prevalence in Aboriginal communities is critical. Current literature on diabetes care for Aboriginal people is primarily focused on remote demographics and overwhelmingly dominated by Western biomedical models and deficit paradigms. This qualitative research project adopted a strengths‐based approach to explore the barriers and enablers to diabetes care for Aboriginal people on Ngarrindjeri Country in rural South Australia.Knowledge Interface methodology guided the research as Aboriginal and Western research methods were drawn upon. Data collection occurred using three yarning sessions held on Ngarrindjeri Country. Yarns were transcribed and deidentified before a qualitative thematic analysis was conducted, guided by Dadirri and a constructivist approach to grounded theory.A total of 15 participants attended the yarns. Major barriers identified by participants were underscored by the ongoing impacts of colonisation. This was combated by a current of survival as participants identified enablers to diabetes care, namely a history of healthy community, working at the knowledge interface, motivators for action, and an abundance of community skills and leadership.Despite the raft of barriers detailed by participants throughout the diabetes care journey, Aboriginal people on Ngarrindjeri Country were found to be uniquely positioned to address diabetes prevalence and management.Health promotion efforts with Aboriginal people on Ngarrindjeri Country must acknowledge the sustained impacts of colonisation, while building on the abundance of community enablers, skills and strengths. Opportunities present to do so by adopting holistic, community‐led initiatives that shift away from the dominant biomedical approach to diabetes care. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the performance of flash glucose monitoring in hospitalized patients requiring intravenous insulin therapy. In this prospective study, an intravenous insulin infusion was adjusted hourly using flash glucose monitoring in hospitalized adults with prednisolone-associated hyperglycemia. The difference in paired point of care (POC) and flash glucose measurements and risk of severe hyper- or hypoglycemia (assessed by Clarke error grid analysis) were assessed. Glucose concentration measured by flash glucose monitoring was lower than POC glucose (mean difference 1.5 mmol/L [27 mg/dL], p < 0.001); however, mean POC glucose was within the target range (9.1 ± 4.1 mmol/L [164 ± 72 mg/dL]) and 97.8% of glucose measurements were within Zone A and B on error grid analysis. Flash glucose monitoring could be used in combination with POC glucose monitoring to minimize the frequency of finger prick blood glucose levels in hospitalized patients prescribed an intravenous insulin infusion. [ABSTRACT FROM AUTHOR]

Recent clinical trials have demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), which were previously only indicated in treatment of type 2 diabetes mellitus (T2DM), can markedly reduce heart failure hospitalisation (HFH), with less striking potential reductions in acute coronary syndromes and cardiac arrhythmias. To evaluate the impact of SGLT2i on cardiovascular outcomes in real-world practice, we performed a retrospective cohort analysis on South Australian (SA) data. A total of 842 individuals with T2DM receiving SGLT2i were identified from SA public hospitals between 2011 and 2019. Episodes of care were temporally matched with those of 3,128 individuals with T2DM not receiving SGLT2i (control). Baseline characteristics were adjusted using inverse probability treatment weighting. The incidence of cardiovascular events at 12 and 24 months was evaluated using coded (International Classification of Diseases, Tenth Revision, Australian Modification [ICD-10-AM]) data. The primary outcome of HFH was lower with SGLT2i use at 12 months (adjusted hazard ratio [HR adj ] 0.44; 95% confidence interval [CI] 0.29–0.68; p<0.001) and 24 months. There were also lower hospitalisations due to acute myocardial infarction (HR adj 0.42; 95% CI 0.21–0.85; p=0.015) and atrial or ventricular arrhythmias (HR adj 0.29; 95% CI 0.14–0.59; p=0.001), with no difference observed in hospitalisation due to ischaemic cerebrovascular events. There was no difference in all-cause mortality at 12 months but interestingly a higher rate at 24 months (HR adj 2.08; 95% CI 1.59–2.72; p<0.001). Despite this, similar reductions in cardiovascular outcomes were observed at 24 months. Use of SGLT2i in patients with T2DM in SA was associated with reductions in cardiovascular events even before their recent Pharmaceutical Benefits Scheme (PBS) listing for heart failure. Furthermore, this analysis supports that SGLT2i play a role not only in HFH reduction but also in reducing coronary and tachyarrhythmic events. This real-world evidence supports the use of SGLT2i as broadly protective cardiovascular drugs. [ABSTRACT FROM AUTHOR]

AIM To assess relationships between continuous glucose monitoring (CGM) time in 70-180mg/dL range (TIR), time below range (TBR), <70mg/dL, time above range (TAR), >180mg/dL and glucose coefficient of variation (CV) in relation to currently recommended clinical CGM targets for older people, which recommend reduced TIR and TBR targets relative to the general type 1 diabetes population. METHODS We conducted a post-hoc analysis using the JDRF Australia Adult Hybrid Closed Loop trial database examining correlations in 120 adults with type 1 diabetes of 3-weeks masked CGM (Guardian Sensor 3; Medtronic) metrics (n=61 on multiple daily injections, 59 on non-CGM augmented pumps) using manual insulin dosing at baseline and at 26-weeks, with 50% randomized to automated insulin dosing (AID). RESULTS Correlations between baseline TIR and TAR were strong (r= -0.966; p<0.0001), weak for TBR (r=0.363; p<0.0001) and glucose CV (r=0.037; p=0.687) while moderate between CV and TBR (r=0.726; p<0.0001). Associations were similar for participants aged >60 years (n=15) vs. younger subjects. Correlations of changes in (∆) TIR with ∆TAR over 26-weeks were strong (r=-0.945; p<0.001) and for ∆TBR were weak (r=0.025; p=0.802). ∆CV did not significantly correlate with ∆TAR (r=-0.064; p=0.526) but did with ∆TBR (r=0.770; p=<0.001) CONCLUSIONS Changes in TIR are not associated with changes in TBR. We therefore suggest that, particularly with AID, while TBR targets in older adults may be prioritized to ensure safety that they should not be linked to TIR but addressed independently. [ABSTRACT FROM AUTHOR]

OBJECTIVE--We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea. This 84-week extension study assessed the long-term safety and efficacy of EQW versus IG. RESEARCH DESIGN AND METHODS--This multicenter, open-label, randomized, two-arm, parallel trial assessed change in A1C, proportions of patients achieving A1C <7.0 and ≤ 6.5%, body weight, incidence of hypoglycemia, and overall safety. RESULTS--Of 415 patients who completed 26 weeks, 390 (194 EQW and 196 IG patients) entered the extension study. At 84 weeks, A1C decreased from baseline (8.3%) by 21.2% for EQW vs. 21.0% for IG (P = 0.029). The proportions of patients who achieved end point A1C targets,7.0 and ≤6.5%were 44.6%for EQWpatients vs. 36.8%for IG patients (P = 0.084) and 31.3%for EQWpatients vs. 20.2%for IG patients (P = 0.009), respectively. Patients taking EQW lost 2.1 kg of body weight, whereas those taking IG gained 2.4 kg (P < 0.001). Among patients taking metformin plus sulfonylurea, the incidence of minor hypoglycemia was 24% for EQW patients vs. 54% for IG patients (P < 0.001); among patients taking metformin alone, it was 8% for EQWpatients vs. 32% for IG patients (P < 0.001). Among adverse events occurring in ≥5% of patients, diarrhea and nausea occurred more frequently (P < 0.05) in the EQWgroup than in the IG group (12 vs. 6% and 15 vs. 1%, respectively). CONCLUSIONS--After 84 weeks, patients treated with EQWcontinued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG. [ABSTRACT FROM AUTHOR]

The article offers information on an open-label randomized study which compared the efficacy of exenatide with insulin glargine titrated to glucose targets in lowering hemoglobin A1c. The study subjects, which involved adults with type 2 diabetes who had suboptimum glycaemic control, were randomly assigned to add exenatide or insulin glargine to their blood-glucose lowering regimens. Presented in details are the findings of the study. It concludes that exenatide is ideal for patients whose risk for hypoglycemia, weight loss and convenience are particular concerns.

Aim: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D). Materials and Methods: This double‐blind, placebo‐controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C‐peptide secretion. Sixty‐four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24‐week, open‐label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C‐peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies. Results: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C‐peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti‐insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups. Conclusions: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti‐insulin antibodies) under temelimab were observed. Markers of β‐cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether relative hyperglycemia was associated with in-hospital mortality in critically ill patients independent of other prognostic variables and whether this association is affected by background glycemia.Design: Prospective observational study.Setting: Mixed medical-surgical ICU in a metropolitan teaching hospital.Patients: From 2,617 admissions to ICU between January 27, 2016, and March 30, 2017, 1,262 consecutive patients who met inclusion and exclusion criteria were studied.Interventions: Glycosylated hemoglobin was used to estimate average glucose concentration over the prior 3 months. Glucose concentration on ICU admission was divided by estimated average glucose concentration to calculate the stress hyperglycemia ratio, an index of relative glycemia. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society.Measurements and Main Results: In this study, there were 186 deaths (14.7%). Admission glucose was significantly associated with mortality in univariate analysis (odds ratio = 1.08 per mmol/L glucose increment; p < 0.001) but not after adjustment for risk of death score (odds ratio = 1.01; p = 0.338). In contrast, stress hyperglycemia ratio was significantly associated with mortality both in univariate analysis (odds ratio = 1.09 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and after adjustment for risk of death score (odds ratio = 1.03; p = 0.014). Unlike admission glucose concentration, stress hyperglycemia ratio was significantly associated with mortality in patients with glycosylated hemoglobin less than 6.5% (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and glycosylated hemoglobin greater than or equal to 6.5% (48 mmol/mol) (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p = 0.005).Conclusions: Unlike absolute hyperglycemia, relative hyperglycemia, as assessed by the stress hyperglycemia ratio, independently predicts in-hospital mortality in critically ill patients across the glycemic spectrum. Future studies should investigate whether using measures of relative hyperglycemia to determine individualized glycemic treatment targets improves outcomes in ICU. [ABSTRACT FROM AUTHOR]

Aim Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients. Materials and methods Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system. Results On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/ L (41.3% ± 5.5% vs 50.0% ± 5.7%, P = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/ L, P = .57) or glucose <4 mmol/ L (2.2% ± 1.1% vs 2.0% ± 1.3%, P = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P = .02) and the insulin dose was increased over time ( P = .02), but the percentage of time outside the 4 to 10 mmol/ L glucose range did not differ over time ( P = .45) or between groups ( P = .24). Conclusions There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia. [ABSTRACT FROM AUTHOR]

The optimal treatment of prednisolone-associated hyperglycaemia is unclear, but guidelines recommend using a body weight-based daily insulin dose. This study evaluated how clinical variables were associated with insulin requirements in hospitalised patients with prednisolone-associated hyperglycaemia. In this prospective study, fifty adult inpatients who were taking prednisolone ≥20 mg/day and experienced hyperglycaemia were prescribed a 24-h intravenous insulin infusion. The daily insulin dose required to attain a mean glucose of 8 mmol/L was calculated. The associations between daily insulin dose and clinical variables were assessed. The participants age was 69 ± 10 years, daily prednisolone dose was 34 ± 10 mg, HbA1c was 7.7 ± 2.0 % (61 ± 10 mmol/mol), 77 % had known type 2 diabetes and 30 % were female. In univariate analysis, weight was associated with daily insulin dose (r2 = 0.11, p = 0.024). A multivariate model comprising sex, HbA1c, a prior diagnosis of diabetes, diabetes treatment and weight explained nearly-two thirds of the variability in daily insulin dose (r2 = 0.65, p < 0.001). In patients with prednisolone-associated hyperglycaemia, calculating insulin doses based on sex, HbA1c, diabetes status and regular diabetes treatment and weight may improve glycaemic control compared to weight-based dosing. [ABSTRACT FROM AUTHOR]

Abstract Background: Previous studies have assessed the efficacy of basal-bolus insulin (BBI) in hospitalized patients by measuring four finger-prick blood glucose levels (BGLs) per day. The aim of this study was to investigate whether this BGL monitoring regimen provides an accurate reflection of glycemia in hospitalized patients administered BBI. We hypothesized that, as three of four readings are preprandial, finger-prick BGLs would underestimate the mean glucose concentration. Subjects and Methods: Twenty-six consecutive consenting subjects with type 1 (n=3) or type 2 (n=23) diabetes mellitus admitted to the hospital and administered insulin glargine once daily and rapid-acting insulin before meals underwent continuous glucose monitoring for up to 72 h. Finger-prick BGLs were performed before each main meal (0700, 1200, and 1700 h) and at 2100 h. Results: Mean daily glucose concentration was not significantly different when assessed by continuous glucose monitoring and finger-prick BGLs (9.6±2.4 vs. 9.6±2.7 mmol/L, P=0.84). A Bland-Altman plot revealed some variability but no bias between the two methods of measurement of glucose concentration. There were 88 postprandial hyperglycemic excursions recorded on continuous glucose monitoring; 61 (69%) were identified by finger-prick BGL monitoring. There were 10 glucose excursions <4 mmol/L during continuous glucose monitoring; only one was detected by finger-prick BGL monitoring. Conclusions: Traditional finger-prick BGL monitoring provides a reasonable approximation of mean daily glucose concentration in the majority of hospitalized patients receiving BBI but underestimates the prevalence of postprandial hyperglycemia and hypoglycemia. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study was to assess the effect of long-term prednisolone on fasting and post-glucose load glucose concentration in patients with inflammatory rheumatological disease. We hypothesized that prednisolone would predominantly increase post-glucose load glucose concentration and that fasting glucose would have poor sensitivity as a screening test for diabetes in patients receiving chronic prednisolone therapy.Methods. In a cross-sectional study of subjects with inflammatory rheumatological disease but without known diabetes, 60 subjects [age = 70 (±10) years, 62% female] who were receiving chronic (>6 months) prednisolone [6.5 (±2.1) mg/day] (Group 1) and 58 controls [age = 70 (±11) years, 62% female] who had not received oral glucocorticoids for at least 6 months (Group 2) underwent an oral glucose tolerance test.Results. Fasting glucose was significantly lower [5.0 (±0.1) vs 5.3 (±0.1) mmol/l, P = 0.02) and post-glucose load glucose concentration significantly higher [8.0 (±0.4) vs 6.8 (±0.3) mmol/l, P = 0.02] in Group 1 than in Group 2. In a multiple regression analysis, glucocorticoid use (P = 0.004) and log CRP (P = 0.02) were independently associated with fasting glucose, while waist circumference (P = 0.01), but not glucocorticoid use, was independently associated with post-glucose load glucose concentration. A fasting glucose &geq;5.6 mmol/l had 33 and 83% sensitivity for diabetes in Groups 1 and 2, respectively.Conclusion. There is discordance between a reduced fasting and increased post-glucose load glucose concentration in rheumatological patients on long-term prednisolone. Therefore fasting glucose has poor sensitivity to screen for diabetes in prednisolone-treated patients. Treatment of prednisolone-induced hyperglycaemia should be directed at the postprandial period.Trial registration. Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au/, ACTRN12607000540415. [ABSTRACT FROM PUBLISHER]

Background: Few long-term RCTs compare Hybrid Closed Loop (HCL) insulin delivery to manual (non-HCL) insulin dosing in type 1 diabetes (T1D). Objective: To examine glycemic and psychosocial outcomes in adults with T1D using HCL vs. manual insulin dosing with self-monitoring of blood glucose (SMBG) for 6 months. Methods: Adults using multiple daily injections or pumps with SMBG were randomized 1:1 after insulin dose optimization to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was time in target range (70-180mg/dL) with masked CGM during the final 3 weeks. Secondary outcomes included other CGM metrics, HbA1c, treatment satisfaction (DTSQs) and diabetes distress (PAID). Intention to treat analysis was performed with ANCOVA or rank sum test. Results: HCL and control groups were well balanced at baseline (Table). At 26 weeks, mean (95% CI) CGM time in range with HCL was greater by 14.8% (11.1, 18.5), with reduced high and low glucose time, and lower HbA1c. There were no between-group differences in treatment satisfaction or diabetes distress (Table). Conclusions: HCL provided a significant and sustained glycemic benefit compared with standard therapy. Results will inform potential users and health professionals and a cost-benefit analysis may facilitate HCL access. Disclosure: S.A. McAuley: Advisory Panel; Self; Medtronic. Research Support; Self; Medtronic, Roche Diabetes Care. Speaker's Bureau; Self; Lilly Diabetes, Roche Diabetes Care. M.H. Lee: Research Support; Self; Medtronic. Speaker's Bureau; Self; AstraZeneca, Medtronic. B. Paldus: Research Support; Self; JDRF. Speaker's Bureau; Self; Australian Diabetes Society, Medtronic. S. Vogrin: None. M.B. Abraham: Speaker's Bureau; Self; Lilly Diabetes. L. Bach: None. M. Burt: None. N. Cohen: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes. Research Support; Self; Ypsomed AG. Speaker's Bureau; Self; Novo Nordisk A/S. P.G. Colman: None. E.A. Davis: None. C. Hendrieckx: None. M. de Bock: None. J. Holmes-Walker: None. J. Kaye: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. K. Kumareswaran: None. R. MacIsaac: None. R.W. McCallum: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. J. Speight: Research Support; Self; Abbott, AstraZeneca, Medtronic, Sanofi-Aventis. Speaker's Bureau; Self; American Diabetes Association, Australian Diabetes Society, Roche Diabetes Care. S. Stranks: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Sanofi-Aventis. S. Trawley: None. V. Sundararajan: None. G. Ward: None. A.C. Keech: Advisory Panel; Self; Amgen, Kowa Research Institute, Inc. Consultant; Self; Sanofi-Aventis. Speaker's Bureau; Self; Abbott, Amgen. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. T. Jones: Other Relationship; Self; Medtronic. D.N. ONeal: None. [ABSTRACT FROM AUTHOR]