Twice-daily Basal Insulin Research Articles

Effect of switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL (Gla-300) in Brazilian people with type 1 diabetes

BackgroundLow adherence to the number of insulin injections and glycemic variability are among the challenges of insulin therapy in type 1 diabetes (T1D). The TOP1 study investigated the effect of switching from twice-daily (BID) basal insulin to once daily (OD) insulin glargine 300 U/mL (Gla-300) on glycemic control and quality of life.MethodsIn this 28-week, phase 4 trial, people with T1D aged ≥ 18 years, who were treated with BID basal insulin in combination with prandial rapid-acting insulin for at least 1 year, and had HbA1c between 7.5% and 10.0%, were switched to Gla-300 OD as basal insulin. The present study aimed to evaluate the impact of this change on HbA1c, glycemic profile, treatment satisfaction and safety. The change in HbA1c from baseline to Week 24 was the primary endpoint.ResultsOne hundred and twenty-three people with T1D (mean age 37 ± 11 years; 54.5% female) were studied. The disease duration was 20.0 ± 9.8 years, baseline HbA1c and fasting plasma glucose (FPG) were 8.6 ± 0.7% and 201 ± 80.3 mg/dL, respectively. After switching from BID to OD insulin regimen, no significant change in HbA1c was observed from baseline to Week 24 (p = 0.873). There were significant reductions in fasting self-monitoring blood glucose (SMBG) from baseline to Week 24 (175 ± 42 vs. 156 ± 38 mg/dL; p < 0.0001), and in glycemic profile (8-point SMBG) at several time points. There was a significant decrease in the proportion of patients with at least one hypoglycemic event (p = 0.025), in numbers of hypoglycemic events per patient-years of any type (p = 0.036), symptomatic (p = 0.007), and confirmed ≤ 70 mg/dL events (p = 0.049) from run-in to the last 4 weeks on treatment. There were significant improvements in treatment satisfaction (p < 0.0001), perceived hyperglycemia (p < 0.0001) scores and satisfaction with the number of injections between post-run-in and Week 24, and a significant decrease in fear of hypoglycemia.ConclusionsSwitch from BID basal insulin to OD Gla-300 as part of basal bolus therapy in T1D resulted in similar glycemic control as measured by HbA1c, but provided significant improvements in SMBG, daily glucose profile, a lower incidence of hypoglycemia and increased patient satisfaction.Trial registrationNCT03406000.

Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trial

Insulin icodec (icodec) is a once-weekly basal insulin currently under development. ONWARDS 2 aimed to assess the efficacy and safety of once-weekly icodec versus once-daily insulin degludec (degludec) in basal insulin-treated type 2 diabetes. This 26-week, randomised, open-label, active-controlled, multicentre, treat-to-target phase 3a trial was conducted in 71 sites in nine countries. Eligible participants with type 2 diabetes inadequately controlled on once-daily or twice-daily basal insulin, with or without non-insulin glucose-lowering agents, were randomly assigned (1:1) to once-weekly icodec or once-daily degludec. The primary outcome was change from baseline to week 26 in HbA1c; the margin used to establish non-inferiority of icodec compared with degludec was 0·3 percentage points. Safety outcomes (hypoglycaemic episodes and adverse events) and patient-reported outcomes were also assessed. The primary outcome was evaluated in all randomly assigned participants; safety outcomes were evaluated descriptively based on all randomly assigned participants who received at least one dose of trial product, with statistical analyses based on all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04770532, and is now complete. Between March 5 and July 19, 2021, 635 participants were screened, of whom 109 were ineligible or withdrew, and 526 were randomly assigned to icodec (n=263) or degludec (n=263). From a mean baseline of 8·17% (icodec; 65·8 mmol/mol) and 8·10% (degludec; 65·0 mmol/mol), HbA1c was reduced to a greater extent with icodec than degludec (7·20% vs 7·42% [55·2 vs 57·6 mmol/mol], respectively) at week 26. This translates to an estimated treatment difference (ETD) of -0·22 percentage points (95% CI -0·37 to -0·08) or -2·4 mmol/mol (95% CI -4·1 to -0·8), demonstrating non-inferiority (p<0·0001) and superiority (p=0·0028). The estimated mean change from baseline to week 26 in bodyweight was +1·40 kg for icodec and -0·30 kg for degludec (ETD 1·70 [95% CI 0·76 to 2·63]). Overall rates of combined level 2 or level 3 hypoglycaemia were less than one event per patient-year of exposure for both groups (0·73 [icodec] vs 0·27 [degludec]; estimated rate ratio 1·93 [95% CI 0·93 to 4·02]). Overall, 161 (61%) of 262 participants receiving icodec and 134 (51%) of 263 participants receiving degludec experienced an adverse event; 22 (8%) and 16 (6%), respectively, experienced a serious adverse event. One serious adverse event (degludec) was assessed as being possibly related to treatment. No new safety issues were identified in relation to icodec compared with degludec in this trial. Among adults with basal insulin-treated type 2 diabetes, treatment with once-weekly icodec versus once-daily degludec demonstrated non-inferiority and statistical superiority in HbA1c reduction after 26 weeks, associated with modest weight gain. Overall rates of hypoglycaemia were low, with numerically but not statistically significantly higher event rates of level 2 or level 3 hypoglycaemia with icodec versus degludec. Novo Nordisk.

PSUN258 New-Onset Ketosis-Prone Diabetes (A- β+) Associated with Covid-19: A Unique Form of Atypical Diabetes

Abstract Since the beginning of the Covid-19 pandemic in December 2019, much has been written about its bidirectional prognostic association with newly diagnosed diabetes, which can either be precipitated new-onset or unmasked previously undiagnosed diabetes, both often presenting as diabetic ketoacidosis. Various mechanisms have been proposed, including stress- or drug-induced hyperglycemia, proinflammatory direct and indirect effects on insulin secretion and activity, as well as direct viral cytolytic effect on the pancreatic β cells via action on the ACE2 receptor integral to islet cell homeostasis. We present a case of a 51-year-old normosthenic male with no known comorbidities, who came in with 2-day history of nausea and epigastric discomfort along with progressively worsening dyspnea and nonproductive cough. He tested positive for Covid-19 by TMA, with elevated acute-phase reactants (CRP and ferritin), and had received his first dose of Covid vaccine 10 days prior. Further evaluation was consistent with diabetic ketoacidosis (glucose 487 mg/dL, pH 7.22, anion gap 27, HCO3 10 mmol/L, beta-hydroxybutyrate 9.71 mmol/L) with concurrent pancreatitis (lipase 2327 U/L, no leukocytosis, lactate 1.41 mmol/L) and acute kidney injury (EGFR 58). His BMI at presentation was 26 kg/m2 with a hemoglobin A1c of 16.9, and no personal history of diabetes. His father and paternal grandmother both had type 2 diabetes. He was managed with hydration and insulin drip titrated as per protocol, with subsequent resolution of DKA and transition to subcutaneous basal-bolus insulin on the second hospital day. Mild-moderate respiratory Covid symptoms improved with dexamethasone, remdesivir, and oxygen supplementation via nasal cannula. Glucose was controlled throughout the hospital stay, and he was discharged improved on the fifth hospital day with twice-daily basal insulin. When he presented to the DKA clinic for follow-up five months post-hospital discharge, his HbA1c was remarkably down to 7.1. There was no evidence of any macrovascular or microvascular complications. GAD-65 and islet cell antibodies were negative. Given good glucose control and adequate β cell function as confirmed by C-peptide level of 3.50 ng/mL, we were hence able to further decrease his basal insulin to once daily and start metformin. With an increasing number of reports of patients with new-onset DKA following Covid-19 infection, without a typical phenotype of type 1 diabetes, it is possible that Covid-19 is associated with a unique form of provoked A- β+ Ketosis Prone Diabetes (KPD). Identical to our case, patients belonging to this subgroup resemble type 2 diabetes patients in that they have adult-onset diabetes, are overweight or obese, lack islet autoantibodies and have substantial β cell functional reserve measured shortly after the index episode of DKA. Awareness of this phenomenon is important as it can help guide a unique treatment path for these patients and avoid injudicious use of insulin moving forward. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Impact of Switching from Twice-Daily Basal Insulin to Once-Daily Insulin Glargine 300U/mL in People with Type1 Diabetes on Basal-Bolus Insulin: Phase4 OPTIMIZE Study.

IntroductionOPTIMIZE evaluated the efficacy, safety and treatment satisfaction of insulin glargine 300 U/mL once daily (Gla-300 OD) in people with type 1 diabetes mellitus (T1DM) previously uncontrolled on basal insulin twice daily (BID) as part of basal–bolus therapy.MethodsOPTIMIZE was a 28-week, prospective, interventional, single-arm phase 4 trial in adults with T1DM. At baseline, basal insulin BID treatment was switched to Gla-300 OD titrated to a fasting self-monitored blood glucose target of 4.4–7.2 mmol/L (80–130 mg/dL). The primary endpoint was the mean glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary endpoints included self-monitored blood glucose, fasting-plasma glucose, hypoglycaemia and patient-reported outcomes including the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs).ResultsSwitching to Gla-300 OD significantly improved mean HbA1c (8.54% at baseline and 8.27% at week 24 [last observation carried forward, N = 94, p < 0.0001]; mean difference 0.27% [95% CI 0.15, 0.40]). There was a statistically significant decrease in fasting self-monitored blood glucose during the study (analysis of variance for repeated measures, p = 0.014; N = 72). Eight-point self-monitored blood glucose was significantly improved between baseline and week 24 for post-breakfast (p = 0.009), post-dinner (p = 0.009) and bedtime (p = 0.049) values. The study did not allow for any significant effects on confirmed and/or severe hypoglycaemia at the ≤ 3.9 mmol/L [≤ 70 mg/dL] or < 3.0 mmol/L [< 54 mg/dL] blood glucose cut-offs to be observed. Statistically significant improvements were observed in DTSQs total scores from baseline (24.1) to week 24 (29.4, p < 0.0001).ConclusionsA basal–bolus regimen including Gla-300 OD was associated with improvements in HbA1c and treatment satisfaction in people with uncontrolled T1DM previously receiving basal–bolus insulin including a basal insulin BID analogue.Trial RegistrationEudraCT number: 2015-001186-46.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-00749-1) contains supplementary material, which is available to authorized users.

Impact of Switching from Twice-Daily Basal Insulin to Once-Daily Insulin Glargine 300 U/mL (Gla-300) in Patients with Type 1 Diabetes (T1DM)—Phase 4 OPTIMIZE Study, Belgian Cohort

The 28-week, prospective, multicenter, open-label OPTIMIZE study, conducted in Belgium and Canada, evaluated treatment optimization with once-daily (OD) Gla-300 in combination with a prandial rapid-acting insulin analog in adults with T1DM previously uncontrolled (HbA1c 8-10%) on twice-daily (BID) basal insulin as part of basal-bolus therapy. The intent-to-treat (ITT) and safety populations of the Belgian cohort comprised 48 patients (52.1% women); mean (SD) age 51.7 (12.8) years and mean (SD) body mass index 28.2 (4.9) kg/m². Prior to the study, 37.5% were on insulin glargine 100 U/mL and 62.5% were on insulin detemir. There was a statistically significant reduction in HbA1c from baseline to month 6 (primary endpoint, p&amp;lt;0.0001). No significant changes were observed in basal or prandial insulin dose, or in total or nocturnal hypoglycemic event rates. Statistically significant improvements were seen in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) total and perceived hyperglycemia scores (p&amp;lt;0.05) (Table), and in the patient satisfaction score for number of injections (p=0.004). Switching from a BID basal insulin analog to OD Gla-300 in this challenging T1DM population was associated with a statistically significant improvement in HbA1c levels and better overall treatment satisfaction. Disclosure C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp &amp; Dohme Corp.. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp.. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott. P. Stella: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Bruhwyler: Other Relationship; Self; Sanofi. K. Alexandre: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi.

A novel approach to basal-bolus insulin initiation in adults with newly diagnosed type 1 diabetes: an observational cohort study of a service redesign

Aims: The National Institute for Health and Care Excellence (NICE) recommendation for insulin in newly diagnosed type 1 diabetes is a ‘basal-bolus’ regimen of prandial insulin with twice-daily basal insulin initiated at diagnosis. We developed an insulin initiation programme that embraces the contribution of endogenous insulin to glycaemic control in adults newly diagnosed with type 1 diabetes. Our aim was to embed carbohydrate counting skills and dose adjustment very early on to mitigate against the decline in glycaemic control that is commonly seen post honeymoon.Methods: We designed a novel insulin initiation programme that focused initially on prandial insulin replacement using the lowest possible dose of basal insulin. The approach also facilitates carbohydrate counting and bolus insulin dose adjustment behaviours from diagnosis.Results: Prior to implementing the new programme, the mean HbA1c at 12 months was 64 mmol/mol (8.0%) (95% CI 60 to 69 (7.6% to 8.4%)). This reduced to 55 mmol/mol (7.1%) (95% CI 51 to 58 (6.9% to 7.4%)), p&lt;0.001 with the new programme. The improved HbA1c persisted to 3 years of follow-up (p&lt;0.001). There were no episodes of diabetic ketoacidosis or severe hypoglycaemia associated with this novel approach.Conclusions: We suggest that using minimal basal insulin and focusing on prandial bolus insulin replacement in adults newly diagnosed with type 1 diabetes is safe, more physiological and may be better able to achieve lasting glycaemic control than the currently proposed national guidelines. This approach will need to be tested formally in an adequately designed randomised controlled clinical trial.

Basal and Bolus Insulin Dose Changes after Switching Basal Insulin to Insulin Degludec in Patients with Type 1 DiabetesMellitus: A Pilot Study.

Ultra-long-acting insulin degludec (DEG) has a longer duration of action and less daily variability relative to other basal insulin (BI), and thus may benefit patients with type 1 diabetes mellitus (T1DM). We examined the impact of switching BI to DEG on glycemic control and insulin dose in T1DM. T1DM patients (n=22; six male; mean age: 64.5±12.6years) receiving basal-bolus insulin therapy were included. Initially, the BI dose was replaced with DEG in a 1:1 ratio; 80-100% of the total dose was replaced with DEG for multiple basal insulin injections. DEG was titrated according to study protocol. Changes in HbA1c, daily insulin dose, glycemic self-monitored blood glucose variations, and hypoglycemia frequency were evaluated for 24weeks. Once-daily DEG significantly decreased HbA1c levels when switched from once-daily BI (7.9±0.8 vs. 7.5±0.9%, p=0.020) and maintained HbA1c when switched from twice-daily BI (8.5±1.6 vs. 8.4±1.2%, p=0.457). The BI dose decreased by -7.8±13.9% (p=0.017) and -16.6±16.9% (p=0.050) when switched from once-daily BI and twice-daily BI, respectively. The total bolus insulin dose significantly decreased when switched from once-daily BI (21.7±8.3 to 19.3±8.8 U/day, p=0.016) especially in the injection before breakfast and evening meal. Body weight and hypoglycemia frequency was not significantly different. DEG improved glycemic control when switched from once-daily BI and maintained glycemic control when switched from twice-daily BI without increasing hypoglycemia.

Type 1 diabetes in adults: new NICE guidance on diagnosis and management

Type 1 diabetes in adults: new <scp>NICE</scp> guidance on diagnosis and management

Switching from Twice-Daily Basal Insulin Injections to Once-Daily Insulin Degludec Injection for Basal-Bolus Insulin Regimen in Japanese Patients with Type 1 Diabetes: A Pilot Study.

The aim of this study was to investigate the efficacy of insulin degludec used for basal-bolus insulin regimen after switching from twice-daily basal insulin in Japanese patients with type 1 diabetes mellitus. The subjects were 22 type 1 diabetes patients treated with basal-bolus insulin regimen with twice-daily basal insulin. Basal insulin was switched to once-daily injection of insulin degludec with 10% dose reduction. HbA1c and fasting plasma glucose (FPG) were measured before and 12 weeks after switching. The frequency of hypoglycemic episodes, standard deviation (SD) of blood glucose, and mean of daily difference (MODD) were evaluated by continuous glucose monitoring (CGM) before and 4 weeks after switching. HbA1c and FPG before and 12 weeks after switching were comparable (HbA1c 8.5 ± 1.4 versus 8.7 ± 1.6%, P = 0.28; FPG 203.2 ± 81.2 versus 206.5 ± 122.4 mg/dL, P = 0.91). The frequency of hypoglycemia during nighttime was not significantly different at 4 weeks after switching (14.4 ± 17.0 versus 11.1 ± 15.0%, P = 0.45). In addition, SD and MODD before and 4 weeks after switching were also comparable. In conclusion, glycemic control under once-daily insulin degludec injection was almost comparable to that under twice-daily basal insulin injections in Japanese type 1 diabetes patients. This study was registered with ID: UMIN000010474.

Effects of Switching from Insulin Glargine or Detemir to Insulin Degludec in Patients with Type 1 Diabetes Mellitus

IntroductionInsulin degludec is a new, ultra-long-acting basal insulin. The aim of this study was to analyze the changes of basal insulin dose and blood glucose profile in basal–bolus therapy of type 1 diabetes mellitus (T1DM) at the switching of basal insulin from insulin glargine or detemir to insulin degludec.MethodsSixteen patients with T1DM were enrolled. The patients underwent continuous glucose monitoring before and after the switching of insulin glargine or detemir to degludec. Ten patients treated with insulin glargine or detemir twice daily, were switched to insulin degludec with 80–90% of the prior insulin dose. The remaining six patients treated with insulin glargine once daily, were switched to insulin degludec without down titration. The changes of daily insulin dose and glycated hemoglobin (HbA1c) were also examined for 12 weeks after switching to insulin degludec.ResultsIn the patients switched from twice-daily basal insulin, no significant difference was found between before and after switching in the blood glucose profile. In the once-daily group, blood glucose levels showed a tendency to decrease after switching to the degludec treatment. During the study period, total daily insulin dose (TDD) and total daily basal insulin dose (TBD) decreased significantly in the twice-daily group, and TDD and TBD showed a tendency to decrease after switching to degludec in the once-daily group. In both groups, the changes of HbA1c were not significantly different.ConclusionIt is possible to achieve similar glycemic control with once-daily injection and lower doses of insulin degludec in patients with T1DM who have been treated with insulin glargine or detemir.

Insulin glargine and its place in the treatment of Types 1 and 2 diabetes mellitus

Insulin treatment in Type 1 and Type 2 diabetes has come a long way since its discovery by Banting and Best in 1922. Early insulin therapy was life-saving, but was associated with practical problems and had side effects such as lipoatrophy. Initial modifications of insulin structure produced several classes of insulins with varying pharmacokinetics, but did not sufficiently mimic physiological insulin release. Novel long- and short-acting insulin analogues, the so-called ‘designer insulins’, developed through genetic engineering in the 1990s, paved the way for more physiological insulin therapy, which was theoretically less problematic in terms of hypoglycaemia and patient satisfaction. Insulin glargine (glargine) was the first DNA-recombinant long-acting insulin analogue. The replacement of asparagine with glycine and the addition of two arginine molecules in the molecular structure results in modified pharmacokinetics. Consequently, glargine has a longer, often 24-h profile, which is described as ‘peakless’ compared with other insulins such as neutral protamine Hagedorn insulin (NPH) and insulin ultralente. Since its launch, the use of glargine in Type 1 and Type 2 diabetes has been extensively reviewed to determine its place in the current insulin market. A potential advantage of glargine seems to be a lower risk of hypoglycaemia, particularly at night. The UK National Institute of Clinical Excellence has recommended that glargine is a treatment option for people with Type 1 diabetes. In Type 2 diabetes, it has been advised that glargine only be considered for: those who require assistance to administer insulin injections; those whose lifestyle is restricted significantly by recurrent symptomatic hypoglycaemic episodes; or those who would otherwise need twice-daily basal insulin injections in combination with oral glucose-lowering drugs.