Basal Insulin Supported Oral Therapy Research Articles

The efficacy of switching basal-bolus insulin therapy to basal insulin-supported oral therapy with a glinide and an α-glucosidase inhibitor in patients with type 2 diabetes depends on insulin secretory capacity, but not on blood glucose profiles and insulin dosages prior to the switching.

We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10mg and voglibose 0.2mg) in Japanese type 2 diabetic patients. Patients who were hospitalized to improve hyperglycemia received basal-bolus insulin therapy. After the reduction of glucose toxicity, a 75g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal-bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70-180mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed. Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups. The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes.

Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT): a multicenter, randomized, open-label, parallel-group study

IntroductionThis study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported...

IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study.

IntroductionIDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group).MethodsAdult patients with T2D diagnosed for at least 12 months and having started IDegLira 2–3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients’ baseline characteristics and the clinical reasons for IDegLira treatment initiation.ResultsOf the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0–20.0) units in the BOT group and 42 (30.0–52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%).ConclusionsIdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients’ outcomes after IdegLira treatment under routine clinical care.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01287-z.

A Smartphone-Based Application to Assist Insulin Titration in Patients Undergoing Basal Insulin-Supported Oral Antidiabetic Treatment.

INSULIA is an insulin-titration app developed for patients with type 2 diabetes treated with basal insulin as part of a basal insulin-supported oral therapy (BOT). The app uses patient-logged fasting blood glucose (FBG) values and a titration plan defined by the treating physician to provide basal insulin dosing recommendations. Physicians use the web portal to monitor their patients' therapy progress and, if necessary, adjust therapy. The aim of this study was to assess the app, specifically its features, handling and impact on diabetes treatment and self-management in Germany. This German retrospective pilot study included physicians (diabetologists, general practitioners, and internists) and patients with type 2 diabetes who either receive or start BOT using the app. Both groups completed group-specific questionnaires between December 2018 and June 2019. Overall, 10 physicians and 34 patients with type 2 diabetes completed their respective questionnaires. Physicians perceived their app-using patients to be more involved and more confident in managing their insulin therapy than patients not using the app. The majority of patients considered the app as a tool that assists with safer insulin treatment. The physicians perceived that due to the app use, FBG and HbA1c target values were achieved more often than patients not using the app and the number and severity of hypoglycemic episodes was reduced. The titration app seems to have a positive impact on BOT patients' FBG and HbA1c target achievement and was highly appreciated by both physicians and patients alike.

Identification of the Inappropriate Clinical Actions (DON'T) to Improve the Management of Patients with Type 2 Diabetes Failing Basal Insulin Supported Oral Treatment: Results of Survey for a Panel of Diabetes Specialists in Italy.

IntroductionDespite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT).MethodsA panel of diabetes specialists was assembled to identify a list of ten corrective actions, “things not to do,” for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration.ResultsA total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues—do not neglect the use of innovative glucose-lowering agents; (2) do not underestimate the risk of lack of hypoglycemia awareness; (3) do not underestimate the benefit of personalization of therapy; (4) do not delay insulin intensification; (5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia; (2) do not underestimate whether the patient has understood the modification of therapy; (3) do not prescribe injection therapy without adequately instructing the patient to titrate it; (4) do not ignore the patient’s adherence; (5) do not stop listening to the patient and verify learning.ConclusionA set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients’ needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes specialists to provide high-value diabetes care.

Delphi-Based Consensus on Treatment Intensification in Type 2 Diabetes Subjects Failing Basal Insulin Supported Oral Treatment: Focus on Basal Insulin + GLP-1 Receptor Agonist Combination Therapies.

IntroductionThe aim of this study was to elaborate a consensus on treatment intensification strategies in patients with type 2 diabetes failing basal insulin supported oral therapy (BOT). The panel focused on glucagon-like peptide-1 receptor agonists (GLP-1RA) and basal insulin (BI) combinations.MethodsThe authors developed a Delphi questionnaire organized into ten statements and 77 items that focused on: the definition of BOT and BOT failure, intensification strategies, fixed-dose combinations in general and the BI/GLP-1RA fixed combination. The survey was administered in two rounds to a panel of 80 Italian diabetes specialists, who rated their level of agreement with each item on a 5-point Likert scale. Consensus was predefined as > 66% of the panel agreeing/disagreeing on any given item.ResultsConsensus was achieved for 71 of the 77 items. The panel agreed that the use of sulfonylureas in the BOT regimen is inappropriate. BOT failure was defined as individualized targets not being met for glycated hemoglobin, fasting plasma glucose and/or postprandial plasma glucose. There was agreement that postprandial hyperglycaemia and/or presence of nocturnal hypoglycaemia or weight gain define BOT failure. Addition of a GLP-1RA to BI therapy was considered to be the best option for BOT intensification. There was consensus for the use of BI/GLP-1RA fixed combinations as valuable options to increase compliance and safely improve glycaemic control. The panel agreed in considering the fixed-ratio combination insulin degludec/liraglutide (IDegLira) to be preferable to the fixed-ratio combination insulin glargine/lixisenatide (iGlarLixi) in the control of glycaemia, body weight and cardiovascular risk.ConclusionAccording to this Delphi consensus, the addition of a GLP-1RA may be the best option to intensify BOT. The BI/GLP-1RA fixed combinations may increase compliance and optimize the advantages of each of these molecules.

Effectiveness and safety of insulin glargine 300 U/mL in insulin-naïve patients with type 2 diabetes after failure of oral therapy in a real-world setting.

AimTo evaluate the effectiveness and safety of initiating basal insulin‐supported oral therapy (BOT) with insulin glargine 300 U/mL (Gla‐300) in patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs (OADs).Materials and MethodsThis non‐interventional, multi‐centre, prospective 52‐week study, conducted in Germany and Switzerland, documented patients with type 2 diabetes with an HbA1c of between 7.5% and 10.0%, currently treated with OADs, after the physician had decided to start a BOT regimen with Gla‐300. The primary endpoint was the rate of achievement of the individualized predefined HbA1c target.ResultsOf 1748 patients included, 1153 comprised the full analysis set, of whom 721 completed documentation of 12 months of Gla‐300 treatment. Twelve months after starting Gla‐300, 49.9% achieved their individualized HbA1c target, and 61.1% achieved either their HbA1c target or a fasting plasma glucose (FPG) of ≤110 mg/dL. Mean HbA1c decreased by −1.22% ± 1.05% to 7.28% ± 0.92% and mean FPG by −51.5 (±48.63) mg/dl to 132.9 ± 33.0 mg/dL. Median duration of HbA1c target achievement was 341 days and probability to remain on target after 6 months was 81%. Hypoglycaemia incidence and rates remained low after 12 months of Gla‐300 treatment; no severe or severe nocturnal hypoglycaemia was observed. Body weight remained unchanged.ConclusionsStarting a BOT regimen with Gla‐300 allowed about 60% of 721 German and Swiss patients with inadequately controlled type 2 diabetes to achieve glycaemic control within 12 months in daily clinical practice. Glycaemic control was achieved without weight gain or increased risk of nocturnal or severe hypoglycaemia.

Switching to Insulin Glargine 300 U/mL (Gla-300) Improves Glycemic Control and Reduces Nocturnal Hypoglycemia in Patients (Pts) with Type 2 Diabetes (T2DM) on Basal Insulin Supported Oral Therapy (BOT)

The prospective observational TOP-2 study investigates the effects of switching pts with T2DM in Germany (n=1,662), Austria and Switzerland, who are uncontrolled (A1c 7.5-10%) on BOT with other basal insulins (BI) to Gla-300 in daily clinical practice. Primary endpoint (EP) is the proportion of pts achieving fasting plasma glucose (FPG) of ≤110 mg/dL after 6 and 12 months, respectively. Secondary EPs include changes in A1c, FPG, body weight (BW) and insulin dose, hypoglycemia incidence and safety. Here we report results of pts recruited at German sites with 12 months results available (n=679). Pts baseline characteristics, efficacy and hypoglycemia EPs are shown in Table 1. Main previous BI was insulin glargine 100 U/mL (Gla-100; 49.2%), most common oral therapy was metformin ± DPP-4 inhibitors (46.4%). At 12 months, proportions of pts at their FPG and A1c targets were 27.0% and 43.2%, respectively. Percentage of pts at FPG and A1c target was max in previous Gla-100 pts (29.3%) and insulin detemir pts (55.3%), respectively. Hypoglycemia rates were low with a trend of >70% reduction of nocturnal hypoglycemia incidence. BW remained stable. In conclusion, switching the BI in a BOT regimen to Gla-300 allowed uncontrolled T2DM pts to reduce their A1c by 0.81% with less nocturnal hypoglycemia and minor BI dose changes. Disclosure J. Seufert: Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH, GI Dynamics Inc.. Research Support; Self; GI Dynamics Inc., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Ipsen Biopharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation. Research Support; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. Research Support; Self; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Self; Sanofi. Research Support; Self; Ypsomed AG. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. H. Anderten: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH, Merck Sharp & Dohme Corp., Eli Lilly and Company, Boehringer Ingelheim GmbH, Pfizer Inc., AstraZeneca, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Takeda. K. Pegelow: Employee; Self; Sanofi-Aventis Deutschland GmbH. S. Pscherer: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. M. Pfohl: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Sanofi.

Initiating Basal Insulin Supported Oral Therapy (BOT) with Insulin Glargine 300 U/mL (Gla-300) Improves Glycemic Control in Patients (Pts) with Type 2 Diabetes (T2DM) without Increasing Hypoglycemia Risk

Toujeo-1, a prospective observational study, investigates the effects of initiating BOT with Gla-300 in insulin-naïve pts with T2DM in Germany (n=1,680) and Switzerland, insufficiently controlled (A1c 7.5-10%) on oral antidiabetic drugs (OADs) in daily clinical practice. Primary endpoint (EP) is the proportion of pts achieving individualized A1c targets after 6 and 12 months, respectively. Secondary EPs include changes in A1c, fasting plasma glucose (FPG), body weight (BW) and insulin dose, hypoglycemia incidence and safety. Here we report results of pts recruited at German sites with 12 months results available (n=674). Pts baseline characteristics, efficacy and hypoglycemia EPs are shown in Table 1. Main OAD treatments were metformin ± DPP-4 inhibitors (49.4%). Twelve months after initiating Gla-300 therapy, proportions of pts at target were 48.4% (A1c at individual target), 30.5% (FPG ≤110 mg/dL), and 60.3% (A1c or FPG at target), respectively. Hypoglycemia rates were low (≤0.events/patient year) and no severe (nocturnal) hypoglycemia was reported. BW remained stable. In conclusion, initiating BOT with Gla-300 allowed insulin-naïve, uncontrolled T2DM pts to reduce their A1c by 1.20% w/o increasing hypoglycemia risk, especially w/o increase in severe (nocturnal) hypoglycemia. Disclosure M. Pfohl: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Sanofi. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. H. Anderten: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH, Merck Sharp & Dohme Corp., Eli Lilly and Company, Boehringer Ingelheim GmbH, Pfizer Inc., AstraZeneca, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Takeda. K. Pegelow: Employee; Self; Sanofi-Aventis Deutschland GmbH. S. Pscherer: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. J. Seufert: Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH, GI Dynamics Inc.. Research Support; Self; GI Dynamics Inc., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Ipsen Biopharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation. Research Support; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH. Research Support; Self; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Self; Sanofi. Research Support; Self; Ypsomed AG.

Changes in Glycemic Control and Body Weight After Initiation of Dapagliflozin or Basal Insulin Supported Oral Therapy in Type 2 Diabetes: A Primary Care Database Study.

Background:The aim was to compare changes in HbA1c and body weight after initiation of dapagliflozin or basal insulin supported oral therapy (BOT) in type 2 diabetes patients in primary care practices.Methods:Patients from 983 primary care practices who started dapagliflozin or BOT between December 2012 and July 2015 (index date, ID) were retrospectively analyzed (Disease Analyzer; Germany). Changes in HbA1c (%) and body weight (kg) were evaluated 90-270 days after ID. Propensity score (PS) matching (1:1) was used to adjust for differences in baseline clinical characteristics (180-0 days before ID: age, sex, health insurance, diabetologist care, glucose lowering therapy, HbA1c, body mass index) and duration (days) between start of therapies and last HbA1c or weight documentation after ID.Results:After PS matching, 766 dapagliflozin (mean ± SD; age: 63 ± 10 years; HbA1c: 8.9 ± 1.2%) and 766 BOT (age: 63 ± 10 years; HbA1c: 8.7 ± 1.1%) patients were included. HbA1c decreased by mean (SD) of 1.0% (1.3) in dapagliflozin and by 1.0% (1.4) in BOT patients after 90-270 days (HbA1c reduction; dapagliflozin vs BOT: –0.01%; P = .79). In 440 dapagliflozin users with available data, body weight (97.4 ± 19.9 kg) decreased by 3.1 (5.8) kg after 90-270 days, whereas no significant weight change was observed in 440 matched BOT patients (97.5 ± 19.9 kg) (weight reduction; dapagliflozin vs BOT: –3.0 kg; P < .05).Conclusions:Initiation of dapagliflozin therapy reduced HbA1c similar to basal insulin with the additional benefit of weight reduction in type 2 diabetes patients treated in general practices.

Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus

The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG < 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% (P < .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients.

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis

ObjectiveTo compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).DesignThis was a network...

Effectiveness and tolerability of treatment intensification to basal-bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study.

BackgroundDue to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT) regimen in T2DM patients in daily clinical practice.MethodsThis noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT).ResultsA total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean −0.94% and −0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean −1.29% and −1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1).ConclusionIntensifying glargine-based BOT or glulisine-based SIT to a BBT regimen in poorly controlled T2DM patients in daily routine care led to marked improvements of glycemic control and was well tolerated.

A reliable serum C-peptide index for the selection of an insulin regimen to achieve good glycemic control in obese patients with type 2 diabetes: an analysis from a short-term study with intensive insulin therapy.

Insulin regimens achieving favorable glycemic control in patients with type 2 diabetes are expected to closely relate to residual insulin secretory ability. We herein attempted to identify a reliable C-peptide immunoreactivity (CPR) index as an insulin secretory marker that would contribute to the selection of an appropriate insulin regimen for patients with type 2 diabetes. We near-normalized blood glucose in 246 obese patients with type 2 diabetes using our protocol (which included short-term intensive insulin therapy, IIT), and administered an oral hypoglycemic agent (OHA). Based on responsiveness to OHA, patients were classified into three therapy groups: non-insulin therapy (n=78), basal-insulin supported oral therapy (BOT) (n=109), and multiple daily insulin injection (MDI) therapy (n=59). Glucagon-loading CPR increment (ΔCPR), fasting CPR (FCPR), CPR2h after breakfast (CPR2h), ratio of FCPR to fasting plasma glucose (CPI), CPI2h after breakfast (CPI2h), and secretory unit of islets in transplantation (SUIT) were assessed with receiver operating characteristic (ROC) and multiple logistic analyses to discriminate the MDI group from the other therapy groups. ROC analysis revealed that CPR2h had the greatest area under the curve and specificity. Multiple logistic analysis identified CPR2h and CPI2h as the most significant explanatory variables for identifying patients assigned to the MDI group. A postprandial serum CPR marker such as CPR2h or CPI2h was shown to be the best index for predicting an appropriate insulin regimen to achieve good glycemic control in obese patients with type 2 diabetes.

Risk of hypoglycaemia in type 2 diabetes patients under different insulin regimens: a primary care database analysis.

Aims: To compare rates and predictors of documented hypoglycaemia in type 2 diabetes patients treated with either basal insulin supported oral therapy (BOT), conventional therapy (CT) or supplementary insulin therapy (SIT) in primary care.Methods: Data from 10,842 anonymous patients (mean age ± SD: 54 ± 8 yrs) on BOT, 2,407 subjects (56 ± 7 yrs) on CT, and 7,480 patients (52 ± 10 yrs) using SIT from 1,198 primary care practices were retrospectively analyzed (Disease Analyzer, Germany: 01/2005–07/2013). Stepwise logistic regression (≥1 documented hypoglycaemia: ICD code) was used to evaluate risk factors of hypoglycemia. Results: The unadjusted rates (95% CI) per 100 patient-years of documented hypoglycaemia were 1.01 (0.80–1.20) (BOT), 1.68 (1.10–2.30) (CT), and 1.61 (1.30–1.90) (SIT), respectively. The odds of having ≥1 hypoglycemia was increased for CT (OR; 95% CI: 1.71; 1.13–2.58) and SIT (1.55; 1.15–2.08) (reference: BOT). Previous hypoglycemia (OR: 11.24; 6.71–18.85), duration of insulin treatment (days) (1.06; 1.05–1.07), history of transient ischemic attack (TIA)/stroke (1.91; 1.04–3.50), and former salicylate prescriptions (1.44; 1.06–1.98) also showed an increased odds of having hypoglycemia. Higher age was associated with a slightly lower odds ratio (per year: 0.98; 0.97–0.99).Conclusions: Insulin naïve type 2 diabetes patients in primary care, initiated with CT and SIT have an increased risk of hypoglycaemia compared to BOT, which is in line with previous randomized controlled trials. As hypoglycaemic events are associated with an increased mortality risk, this real-world finding is of clinical relevance.

Basal insulin combined incretin mimetic therapy with glucagon-like protein 1 receptor agonists as an upcoming option in the treatment of type 2 diabetes: a practical guide to decision making.

The combination of basal insulin and glucagon-like protein 1 receptor agonists (GLP-1 RAs) is a new intriguing therapeutic option for patients with type 2 diabetes. In our daily practice we abbreviate this therapeutic concept with the term BIT (basal insulin combined incretin mimetic therapy) in a certain analogy to BOT (basal insulin supported oral therapy). In most cases BIT is indeed an extension of BOT, if fasting, prandial or postprandial blood glucose values have not reached the target range. In our paper we discuss special features of combinations of short- or prandial-acting and long- or continuous-acting GLP-1 RAs like exenatide, lixisenatide and liraglutide with basal insulin in relation to different glycemic targets. Overall it seems appropriate to use a short-acting GLP-1 RA if, after the near normalization of fasting blood glucose with BOT, the prandial or postprandial values are elevated. A long-acting GLP-1 RA might well be given, if fasting blood glucose values are the problem. Based on pathophysiological findings, recent clinical studies and our experience with BIT and BOT as well as BOTplus we developed chart-supported algorithms for decision making, including features and conditions of patients. The development of these practical tools was guided by the need for a more individualized antidiabetic therapy and the availability of the new BIT principle.

Postprandial serum C-peptide value is the optimal index to identify patients with non-obese type 2 diabetes who require multiple daily insulin injection: Analysis of C-peptide values before and after short-term intensive insulin therapy.

Type 2 diabetes is a progressive disease characterized by a yearly decline in insulin secretion; however, no definitive evidence exists showing the relationship between decreased insulin secretion and the need for insulin treatment. To determine the optimal insulin secretory index for identifying patients with non-obese type 2 diabetes who require multiple daily insulin injection (MDI), we evaluated various serum C-peptide immunoreactivity (CPR) values. We near-normalized blood glucose with intensive insulin therapy (IIT) over a 2-week period in 291 patients with non-obese type 2 diabetes, based on our treatment protocol. After improving hyperglycemia, we challenged with oral hypoglycemic agent (OHA), and according to the responsiveness to OHA, patients were classified into three therapy groups: OHA alone (n=103), basal insulin plus OHA (basal insulin-supported oral therapy [BOT]; n=56) and MDI (n=132). Glucagon-loading CPR increment (ΔCPR), fasting CPR (FCPR), CPR 2h after breakfast (CPR2h), the ratio of FCPR to FPG (CPI), CPI 2h after breakfast (CPI2h) and secretory unit of islets in transplantation (SUIT) were submitted for the analyses. Receiver operating characteristic (ROC) and multiple logistic analyses for these CPR indices were carried out. Many CPR values were significantly lower in the MDI group compared with the OHA alone or BOT groups. ROC and multiple logistic analyses disclosed that post-prandial CPR indices (CPR2h and CPI2h) were the most reliable CPR markers to identify patients requiring MDI. Postprandial CPR level after breakfast is the most useful index for identifying patients with non-obese type 2 diabetes who require MDI therapy.

Treatment duration (persistence) of basal insulin supported oral therapy (BOT) in Type-2 diabetic patients: comparison of insulin glargine with NPH insulin

To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients. This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006. A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29-1.38; unadjusted) and 1.22 (99% CI: 1.18-1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results. Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.