**2. Insulin pump therapy (CSII)**

Continuous Subcutaneous Insulin Infusion (CSII) has been utilized since the 1970s for the treatment of Diabetes Mellitus. The first insulin pumps were extremely large and bulky. Dr. Arnold Kadish devised a backpack insulin pump in the 1960s, but it proved to be less than optimal for everyday use. Dean Kamen in the late 1970s developed a more practical portable insulin pump which was eventually produced by Baxter called the Auto Syringe. This was the initial insulin pump that this author utilized in the early 1908s. Insulin pumps have evolved significantly over the past 40 years becoming smaller, more precise in the delivery of insulin doses and more reliable than their older versions [3]. During the 1980s to early 2000s,

there were several companies providing insulin pumps to the public. Due to varying factors, these companies ceased production and in the late 2000s, there were only 4–5 companies in the US. As of 2018, there are only three large companies still functioning in the USA: Medtronic Diabetes, Omnipod and Tandem. There are several more companies in Europe that are providing insulin pumps. In the future there may be additional entries into the US market from other companies. Patch pumps are of particular interest to many individuals with DM.

The use of continuous subcutaneous insulin infusion as a primary therapy for Type 2 DM patients has been investigated for the past 40 years. It has been utilized in various patient groups, including those who have newly diagnosed Type 2 DM. It is noted that individuals with Type 2 DM have poor to average control [4].

Multiple uncontrolled studies from 2008 to 2013 evaluated insulin pump therapy (CSII) in patients with Type 2 diabetes mellitus. The various studies indicated switching to CSII therapy led to improved glucose control generally, reduction in daily insulin doses compared with conventional Multiple Dose Injection therapy (MDI) and improved patient satisfaction [5]. These studies were conducted in various entities- Clinical Research Centers, Hospital outpatient clinics and small private outpatient offices.

Random Clinical Trials evaluating the efficacy of CSII therapy versus conventional MDI have been conducted and published since 1991 [6–13]. Many of these earlier studies were shorter ranging from 16 to 32 weeks and showed minimal benefit of one modality over the other.

The OpT2mise trial included a large heterogeneous population noted significant benefit compared with MDI with lower HbA1C levels, decrease in insulin requirement and no significant change in weight and no change in hypoglycemic events. This was a large scale multi center international trial which compared the efficacy of CSII therapy to intensive MDI therapy in patients who were not able to reach HbA1C goals despite intensified MDI regimens. This was a randomized parallel group study encompassing a run-in phase, 6-month randomized phase and a 6-month continuation phase. To continue in the trial a minimum of 3 measurements of glucose per day was required [14].

The study noted that CSII therapy significantly improved blood glucoses in patients when compared with MDI regimens (~ mean difference was 0.7%). There was a 20% decrease in the total insulin dose per day with little or no change in hypoglycemic events or weight gain. Additionally, these results also indicate that selection of the proper individual for CSII treatment is paramount. The study also noted that ~ 38% of patients in the CSII treatment arm had mild cognitive impairment. Patients with such impairments can successful implement CSII therapy with proper training and education.

This landmark study of CSII in Type 2 DM individuals does has some notable limitations. Patients with insulin resistance utilizing greater than 220 units per day were excluded. This is a large population which is increasing, and further large studies need to be considered. The study did not include individuals utilizing concentrated forms of insulin (U-200 and U-500).

Additionally, the study does not take in account the availability of continuous glucose monitoring and depended on serum blood glucose (SBG) monitoring. With the advent of flash glucose monitoring and advances in continuous glucose monitoring (CGM) discussed in another part of this chapter, additional studies comparing CSII and MDI in these patients may be warranted.

At present, the CSII systems available for patients with Type 2 DM include pumps with sensor combinations that have the ability to suspend delivery if the sensor notes low glucose [15].

These systems are presently the only ones approved for patients with Type 2 DM.

**101**

may be limited.

treatment regimen between patient visits.

*Newer Modalities in the Treatment of Type 2 Diabetes Mellitus: Focus on Technology*

Future advances in CSII use for Type 2 DM could include the use of the hybrid closed loop system which now available for Type 1 DM individuals. The Medtronic hybrid closed loop system is the only one currently available. This system automatically adjusts the basal delivery every 5 minutes based on sensor readings. The system attempts to maintain glucose levels to an assigned target [16]. This form of CSII therapy functions with two different modes: Auto mode which uses an algorithm to respond to glucose levels. Manual mode is similar to previous pump-sensor combinations and requires preset basal rates by the individual in conjunction with his/her physician. Both systems still require manual meal bolus (MB) administration and manual correction for consistently elevated glucoses. Other companies are presently testing their versions of closed loop hybrid systems which may be avail-

Patient with extreme insulin resistance have been at a disadvantage utilizing CSII

CSII therapy has been considered an improvement over traditional MDI therapy due to multiple factors: (1) There is predictable absorption of insulin. MDI which traditional requires injection of larger doses of insulin will form a depot and generally less efficacious in absorption and metabolic activity compared with CSII which involves smaller volumes [13]. Both the basal rate and meal bolus with CSII can be utilized with more precise insulin increments (tenths or hundredths of units). (2) Patients using CSII therapy appear to have increased satisfaction with this form of insulin therapy compared with traditional MDI injections. Based on personal observation and previous studies, patients find CSII more convenient for their lifestyle, easier to utilize after being trained and more likely to adhere to the treatment regimen. There is less likelihood of omitting (forgetting) their dose of insulin as compare with MDI. Peyrot et al. noted that patients record regular omission of insulin injections [22]. Personal observation of patients within my practice regularly indicates individuals utilizing MDI regularly admit missing meal time insulin injections. Those using CSII therapy note that since the insulin pump is attached and readily available, along with various alarm reminders missing doses is minimal. (3) The ability to download information from insulin pumps to websites (each pump has its own download capability which can cause increase work for the physician) can facilitate more efficient data collection and an ability to change the

Given the advantages of CSII therapy over MDI therapy, it would appear that CSII therapy should be considered for individuals with Type 2 DM as it is now considered for patients with Type 1 DM. However, cost effectiveness in several health systems has not been completely demonstrated. Current policies in many health systems are varied and the ability for patients to obtain access to CSII therapy

therapy due to the restricted capacity of the pumps (either 180 units, 200 units, 300 units). One company in Europe has developed small insulin pumps with 500 unit and 800-unit capacity though this system is presently not available in the United States [18]. Physicians have resorted to utilizing U-500 in the pumps to decrease the frequency of site and pump changes. Several studies have noted the efficacy and improvement in quality of life with the use of U-500 in CSII therapy [19, 20]. Additional attempts to improve glucose control, quality of life, decreasing insulin requirements for Type 2 patients has led to use of so called "double pump" systems, utilizing insulin in 1 pump and pramlintide in an additional pump. Results in a small non-double-blind placebo-controlled observational study indicated a 10–20% decrease in insulin requirements, improvement in glucose control, weight loss and significant improvement in quality of life [21]. Limitations included the ability to obtain supplies for two separate pumps and utilization of pramlintide as this medication in vials was discontinued by the manufacturer at the direction of the FDA.

*DOI: http://dx.doi.org/10.5772/intechopen.84285*

able in the near future [17].

#### *Newer Modalities in the Treatment of Type 2 Diabetes Mellitus: Focus on Technology DOI: http://dx.doi.org/10.5772/intechopen.84285*

Future advances in CSII use for Type 2 DM could include the use of the hybrid closed loop system which now available for Type 1 DM individuals. The Medtronic hybrid closed loop system is the only one currently available. This system automatically adjusts the basal delivery every 5 minutes based on sensor readings. The system attempts to maintain glucose levels to an assigned target [16]. This form of CSII therapy functions with two different modes: Auto mode which uses an algorithm to respond to glucose levels. Manual mode is similar to previous pump-sensor combinations and requires preset basal rates by the individual in conjunction with his/her physician. Both systems still require manual meal bolus (MB) administration and manual correction for consistently elevated glucoses. Other companies are presently testing their versions of closed loop hybrid systems which may be available in the near future [17].

Patient with extreme insulin resistance have been at a disadvantage utilizing CSII therapy due to the restricted capacity of the pumps (either 180 units, 200 units, 300 units). One company in Europe has developed small insulin pumps with 500 unit and 800-unit capacity though this system is presently not available in the United States [18]. Physicians have resorted to utilizing U-500 in the pumps to decrease the frequency of site and pump changes. Several studies have noted the efficacy and improvement in quality of life with the use of U-500 in CSII therapy [19, 20]. Additional attempts to improve glucose control, quality of life, decreasing insulin requirements for Type 2 patients has led to use of so called "double pump" systems, utilizing insulin in 1 pump and pramlintide in an additional pump. Results in a small non-double-blind placebo-controlled observational study indicated a 10–20% decrease in insulin requirements, improvement in glucose control, weight loss and significant improvement in quality of life [21]. Limitations included the ability to obtain supplies for two separate pumps and utilization of pramlintide as this medication in vials was discontinued by the manufacturer at the direction of the FDA.

CSII therapy has been considered an improvement over traditional MDI therapy due to multiple factors: (1) There is predictable absorption of insulin. MDI which traditional requires injection of larger doses of insulin will form a depot and generally less efficacious in absorption and metabolic activity compared with CSII which involves smaller volumes [13]. Both the basal rate and meal bolus with CSII can be utilized with more precise insulin increments (tenths or hundredths of units). (2) Patients using CSII therapy appear to have increased satisfaction with this form of insulin therapy compared with traditional MDI injections. Based on personal observation and previous studies, patients find CSII more convenient for their lifestyle, easier to utilize after being trained and more likely to adhere to the treatment regimen. There is less likelihood of omitting (forgetting) their dose of insulin as compare with MDI. Peyrot et al. noted that patients record regular omission of insulin injections [22]. Personal observation of patients within my practice regularly indicates individuals utilizing MDI regularly admit missing meal time insulin injections. Those using CSII therapy note that since the insulin pump is attached and readily available, along with various alarm reminders missing doses is minimal. (3) The ability to download information from insulin pumps to websites (each pump has its own download capability which can cause increase work for the physician) can facilitate more efficient data collection and an ability to change the treatment regimen between patient visits.

Given the advantages of CSII therapy over MDI therapy, it would appear that CSII therapy should be considered for individuals with Type 2 DM as it is now considered for patients with Type 1 DM. However, cost effectiveness in several health systems has not been completely demonstrated. Current policies in many health systems are varied and the ability for patients to obtain access to CSII therapy may be limited.

*Type 2 Diabetes - From Pathophysiology to Modern Management*

pumps are of particular interest to many individuals with DM.

outpatient offices.

benefit of one modality over the other.

of glucose per day was required [14].

proper training and education.

sensor notes low glucose [15].

concentrated forms of insulin (U-200 and U-500).

ing CSII and MDI in these patients may be warranted.

there were several companies providing insulin pumps to the public. Due to varying factors, these companies ceased production and in the late 2000s, there were only 4–5 companies in the US. As of 2018, there are only three large companies still functioning in the USA: Medtronic Diabetes, Omnipod and Tandem. There are several more companies in Europe that are providing insulin pumps. In the future there may be additional entries into the US market from other companies. Patch

The use of continuous subcutaneous insulin infusion as a primary therapy for Type 2 DM patients has been investigated for the past 40 years. It has been utilized in various patient groups, including those who have newly diagnosed Type 2 DM. It

Multiple uncontrolled studies from 2008 to 2013 evaluated insulin pump therapy

Random Clinical Trials evaluating the efficacy of CSII therapy versus conventional MDI have been conducted and published since 1991 [6–13]. Many of these earlier studies were shorter ranging from 16 to 32 weeks and showed minimal

The OpT2mise trial included a large heterogeneous population noted significant benefit compared with MDI with lower HbA1C levels, decrease in insulin requirement and no significant change in weight and no change in hypoglycemic events. This was a large scale multi center international trial which compared the efficacy of CSII therapy to intensive MDI therapy in patients who were not able to reach HbA1C goals despite intensified MDI regimens. This was a randomized parallel group study encompassing a run-in phase, 6-month randomized phase and a 6-month continuation phase. To continue in the trial a minimum of 3 measurements

The study noted that CSII therapy significantly improved blood glucoses in patients when compared with MDI regimens (~ mean difference was 0.7%). There was a 20% decrease in the total insulin dose per day with little or no change in hypoglycemic events or weight gain. Additionally, these results also indicate that selection of the proper individual for CSII treatment is paramount. The study also noted that ~ 38% of patients in the CSII treatment arm had mild cognitive impairment. Patients with such impairments can successful implement CSII therapy with

This landmark study of CSII in Type 2 DM individuals does has some notable limitations. Patients with insulin resistance utilizing greater than 220 units per day were excluded. This is a large population which is increasing, and further large studies need to be considered. The study did not include individuals utilizing

Additionally, the study does not take in account the availability of continuous glucose monitoring and depended on serum blood glucose (SBG) monitoring. With the advent of flash glucose monitoring and advances in continuous glucose monitoring (CGM) discussed in another part of this chapter, additional studies compar-

At present, the CSII systems available for patients with Type 2 DM include pumps with sensor combinations that have the ability to suspend delivery if the

These systems are presently the only ones approved for patients with Type 2 DM.

is noted that individuals with Type 2 DM have poor to average control [4].

(CSII) in patients with Type 2 diabetes mellitus. The various studies indicated switching to CSII therapy led to improved glucose control generally, reduction in daily insulin doses compared with conventional Multiple Dose Injection therapy (MDI) and improved patient satisfaction [5]. These studies were conducted in various entities- Clinical Research Centers, Hospital outpatient clinics and small private

**100**
