V-Go Insulin Delivery System Versus Multiple Daily Insulin Injections for Patients With Uncontrolled Type 2 Diabetes Mellitus

Type 2 diabetes mellitus affects over 29.1 million Americans, diagnosed and undiagnosed. Achieving and maintaining glycemic control for these patients is of extreme importance when working to prevent complications and improve quality of life for patients. The V-Go is a newly developed insulin delivery system. The push of a button inserts a needle into the patient once daily and remains attached for 24 hours. The V-Go is designed to release a set basal rate throughout the day, while allowing patients to provide up to 36 units of on-demand bolus insulin with the manual click of 2 buttons. It is a spring-loaded device filled daily with rapid-acting insulin that runs without the use of batteries or computer software. The main objective of this prospective active comparator study was to observe the A1C lowering effects of multiple daily insulin injections (MDII) versus the use of the V-Go insulin delivery system for patients with uncontrolled type 2 diabetes mellitus over a 3-month period. In addition, the effect on insulin requirement for these patients was assessed with secondary comparisons of weight, blood pressure, prevalence of hypoglycemic events, and quality of life before and after 3 months of intensified insulin therapy with regular monitoring by a clinical pharmacist at an internal medicine clinic. The average A1C lowering experienced by the 3 patients in the V-Go group was 1.5%, while the average A1C change in the 3 patients in the MDII group was an increase of 0.2%. All patients in the V-Go group experienced a decrease in insulin total daily dose (TDD), with an average decrease of 26.3 units. All patients in the MDII group experienced an increase in insulin TDD with an average of 15 units daily to achieve therapeutic goals individualized for each patient. All patients who underwent intensification of insulin therapy experienced an increase in subjective quality of life (QOL) as determined using the Diabetes-39 (D-39) questionnaire, though QOL results lacked statistical significance.     

Evolving Approaches to Intensive Insulin Therapy in Type 1 Diabetes: Multiple Daily Injections,Insulin Pumps and New Methods of Monitoring

Reviews in Endocrine and Metabolic Disorders -     

Safe and Efficacious Use of Automated Bolus Advisors in Individuals Treated With Multiple Daily Insulin Injection (MDI) Therapy: Lessons Learned From the Automated Bolus Advisor Control and Usability Study (ABACUS)

Numerous studies have shown that use of integrated automated bolus advisors (BAs) provides significant benefits to individuals using insulin pump devices, including improved glycemic control and greater treatment satisfaction. Within the past few years, BA devices have been developed specifically for individuals treated with multiple daily insulin injection (MDI) therapy; however, many clinicians who treat these individuals may be unfamiliar with insulin pump therapy and, thus, BA use. Findings from the Automated Bolus Advisor Control and Usability Study (ABACUS) revealed that BA use can be efficacious and clinically meaningful in MDI therapy, and that most patients are willing and able to use this technology appropriately when adequate clinical support is provided. The purpose of this article is to review key learnings from ABACUS and provide practical advice for initiating BA use and monitoring therapy.     

Overnight versus 24 Hours of Continuous Subcutaneous Insulin Infusion as Supplement to Oral Antidiabetic Drugs in Type 2 Diabetes

Background

Basal continuous subcutaneous insulin infusion (CSII) therapy at a fixed rate may effectively improve glycemic control in patients with type 2 diabetes when oral antidiabetic treatment fails. Regimens of simple constant subcutaneous delivery of insulin may provide theoretical advantages in type 2 diabetes.

Methods

Ten subjects with type 2 diabetes who obtained insufficient glycemic control on oral antidiabetic drugs were included. Following an initial control day, two periods of 3 days with CSII of a rapid-acting insulin analogue, 1.5 IU/h (dose obtained from a preceding study), for 8 hours overnight and for 24 hours, respectively, were carried out in random order. Profiles of serum insulin aspart, serum endogenous insulin, and plasma glucose were recorded.

Results

Compared to the control day, an 8-hour overnight insulin infusion during a 3-day period improved fasting plasma glucose (FPG) (mean differences ± SEM; Δ59.0 ± 10.1 mg/dl; p < 0.01) and 2-hour postprandial plasma glucose (PPPG) (Δ57.8 ± 10.6 mg/dl; p < 0.01) after breakfast. Compared to an 8-hour overnight infusion, a 24-hour infusion further improved all three PPPG values after breakfast, lunch, and dinner (Δ28.8 ± 8.1 mg/dl, Δ30.6 ± 8.1 mg/dl, and Δ35.1 ± 7.9 mg/dl; p < 0.01). During insulin infusion, only one hypoglycemic episode with PG <55.8 mg/dl and mild symptoms was recorded.

Conclusion

Continuous subcutaneous insulin infusion with a rapid-acting insulin analogue at a fixed rate of 1.5 IU/h, either overnight or for 24 hours, improved glycemic control without safety concerns in patients with type 2 diabetes who had secondary failure to oral antidiabetic drugs. The effect on FPG was similar for both treatments, whereas the effect on PPPG was superior when insulin was infused during the entire 24 hours.     

A 16-week open-label, multicenter pilot study assessing insulin pump therapy in patients with type 2 diabetes suboptimally controlled with multiple daily injections

Background

We assessed the efficacy, safety, and patient-reported outcomes (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM) who were suboptimally controlled with a multiple daily injection (MDI) regimen.

Methods

In this subanalysis of a 16-week multicenter study, 21 insulin-pump-naïve patients [age 57 ± 13 years, hemoglobin A1c (A1C) 8.4 ± 1.0%, body weight 98 ± 20 kg, total daily insulin dose 99 ± 65 U, mean ± standard deviation] treated at baseline with MDI therapy with or without oral antidiabetic agents discontinued all diabetes medications except metformin and initiated insulin pump therapy. Insulin was titrated to achieve the best possible glycemic control with the simplest possible dosing regimen. Outcome measures included A1C, fasting and postprandial glucose, body weight, incidence of hypoglycemia, and PROs.

Results

Glycemic control improved significantly after 16 weeks: A1C 7.3 ± 1.0% (−1.1 ± 1.2%, p < .001), fasting glucose 133 ± 33mg/dl (−32 ± 74 mg/dl, p < .005), and postprandial glucose 153 ± 35 mg/dl (−38 ± 46 mg/dl, p < .001). At week 16, the mean daily basal, bolus, and total insulin doses were 66 ± 36, 56 ± 40, and 122 ± 72 U (1.2 U/kg), respectively, and 90% of patients were treated with two or fewer daily basal rates. Body weight increased by 2.8 ± 2.6 kg (p < .001). Mild hypoglycemia was experienced by 81% of patients at least once during the course of the study with no episodes of severe hypoglycemia. There were significant improvements in PRO measures.

Conclusions

Insulin pump therapy using a relatively simple dosing regimen safely improved glucose control and PROs in patients with T2DM who were unable to achieve glycemic targets with MDI therapy. Controlled trials are needed to further assess the clinical benefits and cost-effectiveness of insulin pumps in this patient population.     

The Business of Intensive Insulin Therapy for Type 2 Diabetes Patients: Where It All Began for Me

Ideally, it would be easy for physicians with Diabetes Control and Complications Trial data in hand to convince type 2 diabetes mellitus (T2DM) patients on insulin to move toward intensive insulin therapy (IIT), but in actuality, patient compliance remains a significant issue. One of the statistics that best illustrates this point is that 89% of T2DM patients on insulin do not inject themselves outside of the home (according to the National Health and Nutrition Examination Survey). The market has responded to poor compliance by developing insulin pens and different insulin formulations to improve compliance. But the fact remains that most T2DM patients on insulin are out of control. I would suggest that, in addition to better education, an opportunity exists for a medical device approach to better facilitate an easy-to-use, discreet approach to moving from conventional to IIT.     

Pediatric Smart Insulin Pen Use: The Next Best Thing

In the pediatric population, insulin pump therapy, or CSII, is often considered the gold standard for intensive diabetes management. Insulin pump technology offers families and caregivers many beneficial features including a calculator for insulin dosing and the ability to review diabetes management data to provide data-driven diabetes management. However, for those who find CSII challenging or choose to use multiple daily injections (MDI) there is an option that offers similar features called the Smart Insulin Pen (SIP). Even though SIP technology provides a safe and data-driven diabetes self-management tool for the pediatric population using MDI, there is limited pediatric specific literature. This article will describe current options, data-driven diabetes management, benefits, challenges and clinical use of SIP technology in the pediatric population.     

Combined Pioglitazone and Metformin Treatment Maintains the Beneficial Effect of Short-Term Insulin Infusion in Patients with Type 2 Diabetes: Results from a Pilot Study

Background

The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.

Methods

This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 ± 2 years; body mass index 29 ± 3.2 kg/m²; hemoglobin A1c [HbA1c] 7.6 ± 1.1%) with (1) insufficient glycemic control under a dose of metformin ≥1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual β-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2x 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point.

Results

During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)].Fasting glucose values dropped after insulin infusion (-17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c -6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value -41%, p < .05).Improvements in hsCRP values (postinsulin value, -15%, NS; end value -37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake.

Conclusions

Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.     

Initiating or Switching to Biphasic Insulin Aspart 30/70 Therapy in Subjects with Type 2 Diabetes Mellitus. An Observational Study

OBJECTIVE: To investigate tolerability and glycemic control over 26 weeks in patients with type 2 diabetes (T2D) who initiated insulin with, or switched to, biphasic insulin aspart 30/70 (BIAsp 30) in routine clinical care. METHODS: This was a non-randomized, non-interventional, open-label, observational study involving patients under the care of approximately 150 insulin-prescribing physicians in Denmark. All patients enrolled were prescribed BIAsp 30 in routine care. Starting dose, dose titration and injection frequency were determined individually by each physician. Information on serious adverse drug reactions (SADR), glycemic parameters and hypoglycemic events were obtained from patients’ notes, patients’ diaries and recall, and transferred to case report forms by physicians at baseline (during 4 weeks prior to BIAsp 30 therapy) and after 12 and 26 weeks of treatment. RESULTS: 421 subjects were recruited and 392 provided safety data. The age (mean ± SD) was 62.0 ± 11.4 years, body mass index (BMI) 30.4 ± 6.4 kg/m², duration of diabetes 9.1 ± 8.1 years and HbA1c (%) 9.4 ± 1.7. 199 subjects were prior insulin users and 193 were insulin-naïve patients. Four patients reported a SADR (3 hypoglycemia, 1 severe hypoglycemia). HbA1c was significantly reduced after 26 weeks of BIAsp 30 therapy: prior insulin users -1.2%, insulin-naïve patients -2.2% (both p < 0.001). 28% and 41% of patients, respectively, reached target HbA1c < 7%. Overall the hypoglycemia rate was lower for insulin-naïve patients than for prior insulin users: 5.0 vs. 6.6 episodes/patient-year (p < 0.05). CONCLUSION: Initiating insulin with, or switching insulin to, BIAsp 30 in routine care was safe and effective in patients with T2D.     

Novel Insulin Delivery Profiles for Mixed Meals for Sensor-Augmented Pump and Closed-Loop Artificial Pancreas Therapy for Type 1 Diabetes Mellitus

Maintaining euglycemia for people with type 1 diabetes is highly challenging, and variations in glucose absorption rates with meal composition require meal type specific insulin delivery profiles for optimal blood glucose control. Traditional basal/bolus therapy is not fully optimized for meals of varied fat contents. Thus, regimens for low- and high-fat meals were developed to improve current insulin pump therapy. Simulations of meals with varied fat content demonstrably replicated published data. Subsequently, an insulin profile library with optimized delivery regimens under open and closed loop for various meal compositions was constructed using particle swarm optimization. Calculations showed that the optimal basal bolus insulin profiles for low-fat meals comprise a normal bolus or a short wave. The preferred delivery for high-fat meals is typically biphasic, but can extend to multiple phases depending on meal characteristics. Results also revealed that patients that are highly sensitive to insulin could benefit from biphasic deliveries. Preliminary investigations of the optimal closed-loop regimens also display bi- or multiphasic patterns for high-fat meals. The novel insulin delivery profiles present new waveforms that provide better control of postprandial glucose excursions than existing schemes. Furthermore, the proposed novel regimens are also more or similarly robust to uncertainties in meal parameter estimates, with the closed-loop schemes demonstrating superior performance and robustness.     

Insulin Bolusing Software: The Potential to Optimize Health Outcomes in Type 1 Diabetes Mellitus

Background:

Insulin bolusing calculators alleviate the burden of having to calculate insulin bolus doses for patients with type 1 diabetes mellitus (T1DM). Three important pieces of information are needed: a blood glucose monitoring (BGM) result, carbohydrates to be consumed, and the amount of insulin bolus delivered. The purpose of this study was to describe insulin pump adherence behaviors associated with the use of bolus calculators in youth who use Medtronic insulin pumps.

Methods:

Data were downloaded from the MiniMed Paradigm insulin pumps (Medtronic) of 31 youth with T1DM. Areas of adherence that were evaluated included fundamental insulin pump adherence behaviors (e.g., BGM, carbohydrate entry, and insulin bolusing), decisions about Wizard^® recommendations, and three Wizard steps: BGM result–carbohydrate input–insulin bolus.

Results:

On average, patients conducted BGM ≥4 times/day on 69% of days, inputted carbohydrates ≥3 times/day on 63% of days, and insulin bolused ≥3 times/day on 85% of days. Participants generally followed Wizard recommendations. Finally, participants completed all three Wizard steps (BGM, carbohydrate input, insulin bolus) within 30 min for an average of 29% of boluses. Almost 3% of boluses that were preceded by Wizard use were delivered without conducting BGM or inputting carbohydrates.

Conclusion:

There was substantial variability in insulin pump adherence behaviors (e.g., days when no BGM occurred, reliance on basal insulin). Interventions targeting insulin pump adherence behaviors have the potential to optimize diabetes health outcomes and glycemic control. Improving insulin pump software reports is one promising avenue for improving adherence.     

Patch-Pump Technology to Manage Type 2 Diabetes Mellitus: Hurdles to Market Acceptance

The recent development of novel “patch”-type insulin infusion pump (IIP) technologies has created an opportunity to improve the quality of life for a broader type 2 diabetes patient demographic. At first glance, type 2 diabetes patients represent a large percentage of the total diabetes patient population; however, adoption of traditional IIP products and multiple daily injection (MDI) therapy has remained limited amongst this patient segment. With an insulin reservoir, delivery system, and cannula integrated into a small, wearable, disposable or semidisposable device, patch pumps simplify traditional IIP therapy, while potentially offering therapeutic benefits over traditional MDI therapy. Herein, potential benefits of patch-pump technology for type 2 diabetes patients are considered while outlining the hurdles to broad product adoption that will likely limit the near term commercial opportunity.     

The role of insulin pump therapy for type 2 diabetes mellitus

Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long‐standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin‐pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright © 2016 John Wiley & Sons, Ltd.     

Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: Impact of pump therapy in the OPT2mise trial

Aims

The relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) in type 2 diabetes patients treated with multiple daily injections (MDI) of insulin is poorly documented. In this study, the BHG and PPHG of patients from the OPT2mise study who were initially treated with MDI were assessed before randomization and again after 6 months of continuous subcutaneous insulin infusion (CSII).

Materials and Methods

Blinded continuous glucose monitoring (CGM) data were collected in 259 MDI patients after completion of an 8‐week run‐in period. The hyperglycaemic area under the curve (AUC) during the 24‐hour basal period (AUC‐B) and the postprandial period (AUC‐P) were compared with analysis of variance based on contribution to total hyperglycaemia in HbA1c groups (Group 1, <8%; Group 2, 8%‐8.4%; Group 3, 8.5%‐8.9%; Group 4, 9%‐9.4%; Group 5, ≥9.5%). Changes in AUC‐B and AUC‐P were assessed after 6 months of pump therapy in 131 randomized participants with available CGM recordings.

Results

In patients undergoing MDI therapy, AUC‐B was 21.6% to 54.8% lower in Group 4 to 1 (P = .0138 and P = .0002, respectively) in comparison to Group 5. In contrast, AUC‐P did not differ among HbA1c groups (P = .1009). HbA1c correlated with AUC‐B, but not with AUC‐P. After switching to CSII, AUC‐B and AUC‐P decreased by 21% and 17%, respectively. When comparing responders with non‐responders to CSII therapy, no between‐group differences were observed in AUC‐B and AUC‐P.

Conclusions

Basal hyperglycaemia is the major determinant of overall exposure to hyperglycaemia in type 2 diabetes with MDI failure.     

Impact of dose adjustment for normal eating in Australia (OzDAFNE) on subjective wellbeing, coping resources and negative affects in adults with type 1 diabetes: a prospective comparison study

Aim

This prospective study examined the impact of a structured education program (OzDAFNE) on subjective wellbeing, coping resources, and negative affects in adults with type 1 diabetes. Participants completing the OzDAFNE program were compared to those using continuous subcutaneous insulin (CSII) and multiple daily injections (MDI) over the same time period.

Methods

Participants in the OzDAFNE group (N = 144) were recruited from diabetes centres throughout Australia. The comparison groups were recruited from Diabetes Australia-Victoria's membership database and comprised 383 people using MDI and 64 people using CSII. All participants completed self-report questionnaires at baseline and 12-months later. Additional assessments for OzDAFNE participants were conducted at the end of the education program and at three and six-months following the training.

Results

The results demonstrated that participants completing the OzDAFNE program experienced improved subjective wellbeing (p < .01), a greater sense of mastery and control in managing their diabetes (p < .001), and reduced diabetes-related distress (p < .001) compared to the CSII and MDI groups. However, the CSII group recorded a significant drop in self-esteem (p < .001) over the duration of the study.

Conclusions/Interpretations

The OzDAFNE program provides a powerful mastery experience for participants, positively influencing subjective wellbeing and diabetes-related distress.     

Personalized Medicine for Diabetes: Genetics Factors Contributing to Type 2 Diabetes across Ethnicities

Type 2 diabetes mellitus (T2DM) is among the many common diseases with a strong genetic component, but until recently, the variants causing this disease remained largely undiscovered. With the ability to interrogate most of the variation in the genome, the number of genetic variants has grown from 2 to 19 genes, many with multiple variants. An additional three genes are associated primarily with fasting glucose rather than T2DM. Despite the plethora of new markers, the individual effect is uniformly small, and the cumulative effect explains little of the genetic risk for T2DM. Furthermore, the success is largely restricted to European populations. Despite success in mapping genes in Asian populations, success in United States minorities, particularly African Americans, has been limited. The genetic findings highlight the role of the β cell in diabetes pathogenesis, but much remains to be discovered before genetic prediction and individualized medicine can become a reality for this disease.