Abstract
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.
Keywords
Type 2 diabetes mellitus affects over 29.1 million Americans, or 9.3% of the population, both diagnosed and undiagnosed. The prevalence is growing daily as 1.7 million new cases of type 2 diabetes were diagnosed in 2012 alone. 1 Type 2 diabetes can be associated with many long-term complications, including heart disease, stroke, blindness, kidney disease, and neuropathy. Achieving and maintaining glycemic control for patients with type 2 diabetes is of extreme importance when working to prevent complications and improve quality of life for patients. If glucose control is not achieved with diet, exercise, and oral antidiabetic medications, a majority of patients with type 2 diabetes eventually end up initiating insulin therapy over the course of their treatments, generally starting with basal insulin.
The V-Go is a newly developed insulin delivery system manufactured by Valeritas out of Bridgewater, NJ. While the process of bringing the V-Go to market began in 1999, FDA approval was obtained in December 2010 and the V-Go was launched regionally starting in May of 2012. The V-Go is distributed through retail community pharmacies and coverage has been obtained through commercial prescription insurances and in some cases, through Medicare Part D plans. Filled with rapid-acting insulin daily, the push of a button on the V-Go inserts a 4.6 mm 30 gauge needle into the patient once daily and remains attached for 24 hours at a time. The V-Go, which weighs approximately 1 ounce when filled with insulin, is designed to release a set basal rate throughout the day once the needle is injected, while also allowing patients to provide on-demand bolus insulin with meals or as correction. While some refer to it as a disposable insulin pump, the V-Go is a waterproof, spring-loaded device containing only rapid-acting insulin that runs without the use of batteries or computer software. 2 With the simple click of 2 buttons, the V-Go can administer on-demand bolus insulin in 2 unit increments up to 36 units, or 18 “clicks” in a 24 hours period, eliminating the need for additional injections for bolus insulin delivery. The V-Go is available with a 20, 30, or 40 unit basal delivery, each allowing up to 36 units of bolus insulin. The V-Go is meant to be removed and replaced every 24 hours. 3 Due to its recent integration into type 2 diabetes treatment, the V-Go has had few studies comparing it to other methods of standard basal-bolus insulin delivery.
The SIMPLE Trial was a 12-month study in which researchers observed glycemic control of 89 patients with type 2 diabetes who used a V-Go by comparing changes in A1C. Patients were included if they had an A1C of greater than 7.0% and were divided into 5 different patient groups based on their antidiabetic medication regimens prior to initiation of insulin administration with the V-Go. The mean change in A1C after 3 months for patients initiating V-Go use was a reduction of 0.7%, while an average reduction in insulin total daily dose (TDD) of greater than 11 units was observed, an estimated 18% decrease in TDD. 4
An additional previous independent study assessing V-Go use entitled the UMASS Study compared the outcomes of patients before and after V-Go use. The UMASS Study enrolled 21 patients with uncontrolled type 2 diabetes. 93% of these patients were on insulin glargine prior to V-Go initiation, while 66% of patients were also on rapid-acting insulin. 7 patients discontinued use of the V-Go within the first 2 weeks of the study due to site rash, discomfort, and/or low blood sugar readings. Of the 14 remaining patients, the average length of treatment was 88 days. After approximately 3 months of treatment, the mean A1C change seen was a reduction of 2.4% while the average reduction in insulin TDD was 55 units, or a 46% decrease. Researchers in this study cited potential poor adherence prior to V-Go initiation as a factor influencing their results. 5
The Alegent Creighton Clinic where this study took place is associated with Creighton University and the CHI Health Alegent Creighton Clinics. The clinic employs 2 endocrinologists, 4 internal medicine physicians, as well as a clinical pharmacist and a registered dietician who are both certified diabetes educators (CDE). The diabetes education program at the clinic is accredited through the American Diabetes Association, allowing providers to bill for patient education.
A large number of patients with type 2 diabetes mellitus are uncontrolled (A1C > 7%). This illustrates the need for more intense therapy and additional means to better control blood sugars of patients with T2DM. This study was designed to determine the benefits of using the V-Go insulin delivery device verses multiple daily insulin injections (MDII).
The main objective of this study was to observe the A1C lowering effects of 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 therapy.
Methods
IRB approval for this prospective active comparator study was officially obtained in January of 2014 from the Creighton University and Alegent Investigational Review Boards. Patients of the Internal Medicine providers at the CHI Health Alegent Creighton Dundee Clinic with a diagnosis of type 2 diabetes mellitus were identified with ICD-9 code reports and these patients were screened for inclusion in the study. Patients were required to have uncontrolled blood sugars with an A1C of 8% or greater. Investigators initially looked to enroll patients who were at a point in therapy requiring the addition of meal-time insulin, specifically looking at uncontrolled patients with high basal insulin doses of >0.5 units/kg/day. After patient recruitment was not as high as the researchers had hoped, patient recruitment was expanded to include those with type 2 diabetes who were considered to be good candidates for insulin administration with a V-Go as determined by the patient’s physician in collaboration with clinical pharmacists at the Dundee Clinic. This included patients already on basal-bolus insulin regimens who were uncontrolled or who had adherence difficulties, patients at a point in therapy warranting initiation of meal-time insulin, or insulin naïve patients requiring initiation of insulin therapy. Initial recruitment efforts yielded 8 total participants in the study including 5 patients opting for using the V-Go and 3 patients who either continued or initiated MDII. One patient in the V-Go group ended up dropping out due to skin irritation from the adhesive on the product. This patient was unwilling to utilize various efforts to decrease this discomfort and chose to discontinue use. An additional patient in the V-Go group was lost to follow-up, resulting in a group population of 3.
The study investigators chose to use an A1C goal of > 8% because it was felt that despite patients with an A1C between 7% and 8% being possible candidates for initiation of insulin, there are other classes of antidiabetic medications that have been shown to lower A1C by approximately 1% that researchers thought may be more appealing to patients and would not require as much attention or sacrifice to get an A1C to goal. To maintain consistency between the inclusion criteria of the treatment groups, patients already on insulin therapy with an A1C between 7% and 8% were not included in this study. In addition, patients with type 2 diabetes who also have a cardiovascular comorbidity or advanced age may have a slightly elevated A1C goal and may not be candidates for intensification of therapy.
The clinical pharmacist participating in the study had an established collaborative practice agreement with the physicians at the Alegent Creighton Dundee Clinic, which allowed independent medication management under supervision of clinic physicians. All decisions regarding patient treatment followed current clinic standard of care and utilized collaborative efforts between the physicians and pharmacists to help make decisions relating to identifying patients, altering medication treatment plans, and providing information relating to treatment options.
Once patients were identified by a registered nurse or clinical pharmacist and the patient’s provider agreed that additional therapy should be initiated or that their patient would benefit from insulin administration with a V-Go, the patient underwent their first meeting with a researcher. During this meeting, informed consent was obtained and the patient was given information regarding the 2 options of either initiating, or in some cases continuing insulin administration via multiple daily injections, or initiating use of the V-Go. Based on clinical assessment and patient-specific concerns, a recommendation was made by 1 of the clinical pharmacists, but ultimately the decision of therapy regimen was left up to the patient to ensure patient acceptance and commitment to treatment. At this time, baseline measures were also evaluated. Patients were asked to complete 4 blood glucose readings per day for 1 week prior to initiating the chosen therapy, and were asked to follow this routine for at least 3 months. Patients were asked to take blood sugar readings before each meal in addition to alternating 1 postprandial blood sugar reading daily, chosen by the patient. This helped researchers obtain adequate baseline information for comparison at the end of the study, and helped ensure safe, appropriate, and effective bolus insulin doses were being given. A baseline A1C was also obtained for patients who did not have an accurate recent value. In addition, patients’ baseline weight and blood pressure were obtained, and calculation of the patient’s current total daily dose of insulin (TDD) was done. Finally, patients were asked to complete a diabetes-specific quality of life (QOL) survey called the Diabetes-39 (D-39) questionnaire. The D-39 questionnaire is a self-administered survey that uses a Likert-type scale. Patients were asked 39 questions to assess how affected various aspects of their lives were by their diabetes on a scale of 1 through 7 with 1 being absolutely unaffected and 7 being extremely affected. The 39 questions covered 5 dimensions of QOL, including Diabetic Control (12 questions), Anxiety and Worry (4 questions), Social Burden (5 questions), Sexual Functioning (3 questions), and Mobility and Energy (15 questions). The final 2 questions assessed overall QOL and a subjective rating of disease state severity.
Approximately 1 week after the initial encounter, patients were asked to return to the clinic to discuss and ultimately make their treatment choice. Though all patients approached for the study were identified to be good candidates for the V-Go and it was recommended for them to initiate V-Go use, those in the MDII group ultimately chose not to follow the pharmacist’s recommendation and instead opted for intensified MDII therapy. At the time of this second meeting, patients were prescribed the necessary products correlating to the chosen regimen. Though not a requirement of study participation, patients were encouraged to fill at a pharmacy with trained pharmacists familiar with the V-Go to help eliminate additional confusion. Patients also received additional education regarding the new medication or medication changes, including recognition and treatment of hypoglycemia. Patients were also asked to note the number of hypoglycemic episodes they experienced during the 3-month study phase.
Patients enrolled in the study were managed weekly either via phone or office visit to adjust insulin therapy in an effort to reach therapeutic goals individualized for each patient. Modifications to other antidiabetic medications were not made for any of the patients in this study during the study period. The monitoring included daily blood glucose logs and patient-reported signs and symptoms of hypoglycemia or hyperglycemia. Once patients reached goals with weekly management, they were shifted to a monthly follow-up initiated by the researchers which included the same monitoring parameters. At the end of the 3-month study, an A1C was drawn, and the secondary measurements of insulin TDD, weight, blood pressure, and hypoglycemic events were determined. Patients’ QOL was also assessed again using the D-39 questionnaire.
Results
The primary outcome assessed in this study was the change in A1C after 3 months. The average A1C lowering experienced by patients in the V-Go group was 1.5% after only 3 months of insulin administration using the V-Go. Patients in this group had an average baseline A1C of 9.1% and a 3-month post–study enrollment average A1C of 7.5%. The average A1C change in the MDII group after 3 months of closely monitored insulin therapy was an increase of 0.2%. Two of the 3 patients in this group experienced an A1C reduction, while the third patient saw a 1.9% increase in A1C. The mean baseline A1C for the MDII group was 8.8% and the mean 3-month post–study enrollment A1C was 9.0%. Individual patient results for the V-Go group can be viewed in Table 1 and the MDII group in Table 2.
Patient Results for the V-Go Group—A1C.
Patient Results for the MDII Group—A1C.
Total daily dose of insulin for each study enrollee was also assessed. In the V-Go group, patients started with an average TDD of 73.7 units, and had a final average TDD of 47.3 units. All patients using the V-Go experienced a decrease in insulin 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 (Tables 3 and 4). However, all of these patients were only on basal insulin and initiated meal-time doses at baseline, while the patients in the V-Go group were on basal-bolus regimens at baseline.
Patient Results for the V-Go Group—Insulin TDD.
Patient Results for the MDII Group—Insulin TDD.
On only basal insulin at baseline.
In looking at secondary outcomes, researchers noticed that there was no change in weight for any patient in the V-Go group after 3 months of use. In the MDII group, 1 patient gained 5 pounds, 1 patient lost 1 pound, and the third patient remained weight neutral, essentially deeming these results negligible. Changes in both groups were similar in regards to increases and decreases in both systolic and diastolic blood pressure, essentially rendering this measure inconclusive (see Table 5). When assessing patient-reported hypoglycemic events for both groups, there were no severe reports requiring third party intervention. Two patients in the V-Go group reported or documented more than 1 hypoglycemic event with a blood sugar < 70 mg/dL, resulting in less than 0.2 events per treatment day, but these were always attributed to carbohydrate counting errors or insulin overcorrection as reported by the patient. In the MDII group, no patients reported or documented more than 1 hypoglycemic event with a blood sugar < 70 mg/dL. There were no serious adverse drug events reported during the study period.
Comparison of Insulin Regimens and Biometrics—Baseline and 3 Months.
In assessing QOL information using the D-39 questionnaire, Boyer and Earp 6 recommend using linear transformation of the raw scores to a 0 to 100 scale to better facilitate comparison between the 5 different dimensions of QOL. Neither the pre nor post results were obtained for 1 patient in the MDII group. None of the QOL scores for patients in either group showed statistical significance when scores from the baseline and 3-month post–insulin intensification surveys were compared, though the transformed mean (TM) score for each of the QOL dimensions was lower at the 3-month mark as compared to baseline. The dimension of anxiety and worry neared statistical significance. QOL survey results are outlined in Table 6.
Comparison of Quality of Life (QOL) Survey (D-39 Questionnaire) Results Based on Dimension.
On a 0-100 scale (higher number = lower subjective QOL).
No score recorded at baseline.
To further analyze subjective QOL, descriptive statistics were used to determine which dimension of QOL was most affected by having diabetes. At baseline, the dimension of Diabetes Control most strongly affected QOL, with Anxiety and Worry a close second. The remaining 3 dimensions in descending order of effect on QOL included Energy and Mobility, Social Burden, and Sexual Functioning. At the 3-month mark, the dimensions most affected by having diabetes were determined to be (in descending order) Anxiety and Worry, Energy and Mobility, Diabetes Control, Social Burden, and Sexual Functioning. These results are detailed in Table 7.
Quality of Life (QOL) Results.
On a 0-100 scale (higher number = lower subjective QOL).
Discussion
Overall, the most significant finding from this study was the change in insulin TDD for patients using the V-Go versus MDII. There are many potential explanations for this result in addition to the factors presented by the use of the V-Go. It was suspected that many of these patients had potential adherence concerns before enrolling in the study, and being more closely monitored encouraged better control of their blood sugars and disease state. In addition, it is likely that patients experience better absorption of insulin throughout the day when it is administered in a more physiologic manner as with the V-Go. Patients are also more likely to administer meal-time insulin when using the V-Go given that the device is attached to their person, thus, fewer missed doses help patients obtain better blood glucose control. Patient demographics and lab values were similar at baseline between patient groups allowing for better intergroup comparison as shown in Table 5.
Patients in the V-Go group experienced a greater drop in A1C than those in the MDII group. Though the initial average A1C in the V-Go group was higher (9.1% vs 8.8%), the percentage of A1C reduction seen by individual patients was still greater in the V-Go Group than in patients in the MDII group. Patients in the V-Go group also reported high satisfaction with the new device, and complaints were minimal, if presented at all.
Though patients in the V-Go group did see more frequent decreases in blood pressure than the MDII group, as outlined in Table 8 and Table 9, it is not believed that these results were causative. With a larger patient population, it is possible that more trends may be noted and more conclusions drawn. In addition, there was a lack of consistency when taking patient blood pressures (eg, time of day, stress level, location in the clinic, and study investigator variances) leading researchers unable to draw conclusions based on these measures.
Patient Results for the V-Go Group—Blood Pressure.
Patient Results for the MDII Group—Blood Pressure.
No change.
Patients in the V-Go group maintained consistent weights, while patients in the MDII group fluctuated more. This is not believed to be causative, especially when considering inconsistencies when obtaining values, uncontrollable outside factors affecting patient weight, and the short amount of time between pre- and postobservation.
QOL was improved postinitiation of an intervention to optimize glycemic control in all 5 measured dimensions of QOL. This finding supports the results of many other studies including Hajos et al. 7 Though it is quite possible this increase in QOL could be a result of improved glycemic control, without statistical significance it is difficult to prove causation. The small size of this study did not allow for intricate analysis of the scores.
There were limitations to this study present. Most important to note is the small sample size. Initially, investigators were hoping to target a much larger patient population with uncontrolled type 2 diabetes at this internal medicine clinic. However, due to the fact that the internal medicine physicians practice in the same clinic as 2 endocrinologists, many patients with uncontrolled type 2 diabetes are referred to endocrinology for better management, referred to the clinical pharmacist for between visit follow-up, or have met with the dietician and CDE in the clinic and are on their way to better control. Thus, the number of patients meeting inclusion criteria who were willing to work with researchers was much lower than anticipated. Once these eligible patients were identified, cost became an additional issue for some. The out-of-pocket cost for both treatment options was very much insurance dependent, and researchers often had a difficult time in helping to obtain coverage for the V-Go considering the novelty associated with the device.
The way in which the patient was introduced to the study also created a slight barrier. For some of the patients, a call or visit from a clinical pharmacist they had never met led to hesitancy, even though it was explained that the pharmacist had worked in communion with the patient’s physician and under a collaborative practice agreement. Without existing patient rapport, initiation of or introduction to a new device and/or treatment plan can be understandably difficult. Though patient acceptance was improved when introduction to the study was tied to a physician visit, time constraints made that coordination more difficult.
An additional matter to consider when assessing the results of this study is the fact that both groups of patients were being followed much more closely after enrollment in this study than they may have been at baseline. Patients were also on different insulin regimens and different antidiabetic medications at baseline, leading to additional variability in results.
Conclusions
In conclusion, this study helped show that the V-Go is a viable option for insulin delivery and blood glucose management in patients with uncontrolled type 2 diabetes mellitus. Patients in this study who used a V-Go experienced a reduction in A1C and required less insulin each day when compared to patients using MDII. Patients in both groups who received intensified insulin regimens experienced an increase in subjective QOL for all 5 dimensions assessed using the D-39 questionnaire. Though there are barriers present to V-Go use, such as patient acceptance and insurance coverage leading to increased patient cost, there are still many patients who may be good candidates for this new device. These patients may include those with adherence issues, those who may have questionable absorption of long-acting insulin, patients who require a more physiologic insulin delivery, and those with needle aversion. Additional studies of V-Go use in patients with type 2 diabetes could greatly benefit this patient population, especially when considering QOL before and after initiation. Long-term, larger studies are necessary to further investigate the effect these insulin regimens have on both QOL and glycemic control.
Footnotes
Abbreviations
D-39, diabetes-39; ICD-9, International Classification of Diseases; MDII, multiple daily insulin injections; QOL, quality of life; TDD, total daily dose; CDE, certified diabetes educator.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.