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Insulin is secreted continuously by beta cells in a glucose-dependent manner throughout the day. Betacell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study.
Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus.
Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden. Glucose control and vascular complications in veterans with type 2 diabetes [published corrections appear in N Engl J Med. Standards of medical care in diabetes—2010 [published correction appears in Diabetes Care.
Efficacy and safety of insulin analogues for the management of diabetes mellitus: a metaanalysis. A comparative study of insulin lispro and human regular insulin in patients with type 2 diabetes mellitus and secondary failure of oral hypoglycemic agents. Differences in hypoglycemia event rates and associated cost-consequence in patients initiated on long-acting and intermediate-acting insulin products. Tufts OCW material is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License.
Pain is associated with injection therapy and glucose monitoring, although thinner and shorter needles are now available to help decrease pain. 11 Insulin may be used alone or in combination with oral medications, such as metformin (Glucophage).
In general, analogue insulin is similar to human insulin in controlling diabetes, although some trials have found higher mean A1C levels in patients taking analogue insulin compared with human insulin. One of the most important considerations is the pharmacokinetics of different insulin preparations 26A  (Table 1 26 and Figure 227A ).
Insulin therapy may be started with a set dosage, such as 10 units of glargine daily, or by using weight-based equations. To maximize benefit without causing significant adverse effects, it is important to consider the mechanism of action for different therapies.Insulin sensitizers have been proven safe and effective when combined with insulin therapy.
Glucose tolerance and mortality: comparision of WHO and American Diabetes Association diagnostic criteria.
When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Weight gain associated with insulin therapy is due to the anabolic effects of insulin, increased appetite, defensive eating from hypoglycemia, and increased caloric retention related to decreased glycosuria.
17 Analogue insulin usually causes less postprandial hyperglycemia and delayed hypoglycemia. Equations to estimate augmentation, replacement, carbohydrate ratio, and correction therapy are listed in Table 2.
The needle should be placed at a 90-degree angle to the skin and held in place for five to 10 seconds after injection to prevent insulin leakage. 36,37 Metformin is usually continued indefinitely after the patient starts insulin therapy because it reduces cardiovascular risk in overweight patients with type 2 diabetes.12 Metformin combined with insulin is also associated with decreased weight gain, a lower insulin dosage, and less hypoglycemia compared with insulin alone.
Prospective Diabetes Study, early intensive glucose control starting with a sulfonylurea, then metformin, then insulin was associated with a 25 percent reduction in microvascular complications and a 12 percent risk reduction in any diabetes-related end point, but was not associated with a reduction in all-cause mortality.


18,19 In a recent meta-analysis, glycemic control was not improved with analogue insulin compared with human insulin, but nocturnal hypoglycemia was reduced.17An industry-funded cost-effectiveness analysis found that the increased cost of medication is more than off set by the reduction in hypoglycemic events. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal and 50 percent as bolus, divided up before breakfast, lunch, and dinner.
5 A subgroup of patients randomized to intensive therapy with metformin alone had a 36 percent reduction in all-cause mortality. These medications are safe and effective when combined with insulin.39Insulin secretagogues (sulfonylureas and glitinides) can be combined with insulin, especially when only basal augmentation is being used.
The drug is based on Byetta, an exenatide drug manufactured by Eli Lilly that is already on the market. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing therapy.
Hypoglycemia has been associated with an increased risk of dementia and may have implications in cardiac arrhythmia. 20,21 Cost-effectiveness analyses have differed regarding the long-term cost savings of using analogue insulin in patients with type 2 diabetes, with industry-sponsored studies finding reduced cost22 and government-sponsored studies finding no cost reduction. 5,31A  Current ADA goals for glucose control are outlined in Table 3.16 Fasting glucose readings are used to titrate basal insulin, whereas both preprandial and postprandial glucose readings are used to titrate mealtime insulin. However, there is a possible increased risk of hypoglycemia that needs to be monitored closely. The drug helps the body process glucose, which helps control blood sugar levels in individuals with non-insulin dependent diabetes.
Metformin should be continued if possible because it is proven to reduce all-cause mortality and cardiovascular events in overweight patients with diabetes. 23 Measures of adherence and quality of life have been improved with analogue insulin compared with human insulin. Benefits of insulin pens include the convenience of storing at room temperature for 28 days after opening and ease of use for patients with visual or dexterity problems. Usually by the time insulin is required for meals, insulin secretagogues are not effective or necessary.
Byetta is only one of the drugs used to control Type 2 diabetes, though most drugs are only slightly more effective than proper diet and exercise.
In a study comparing premixed, bolus, and basal insulin, hypoglycemia was more common with premixed and bolus insulin, and weight gain was more common with bolus insulin. American Diabetes Association (ADA) guidelines recommend that the blood glucose level be checked if hypoglycemia is suspected (glucose level lower than 70 mg per dL [3.89 mmol per L]), then treated with a fast-acting carbohydrate, such as juice or glucose tablets. Some physicians have adopted the Treat-to-Target Trial's titration schedule for basal insulin (Table 4).31 It is also safe and effective to give patients autonomy to adjust insulin on their own.
While Type 2 diabetes drugs help, the best way to combat the disease is for individuals to manage it through controlling food intake and getting the right amount of physical activity.The potential dangers of BydureonMuch like Byetta, Bydureon has several potential dangers. Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications.
The blood glucose level should be rechecked after 15 minutes to make sure it has normalized.8An epidemiologic study has raised concern about cancer risk with glargine (Lantus) and other insulin therapies. The FDA has requested at least two more studies on the effects Bydureon may have on user’s heart rates. Accessed December 10, 2010.Type 2 diabetes mellitus is associated with insulin resistance and slowly progressive beta-cell failure.


9 Glargine is theoretically more likely to cause cancer because of its high affinity for insulin-like growth factor I receptor.
Byetta has been known to cause clumsy movements, dizziness, headaches, and changes in behavior and mood.
By the time type 2 diabetes is diagnosed in patients, up to one-half of their beta cells are not functioning properly. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Eli Lilly has been pushing very aggressive sales goals for Bydureon – more than $1 billion per year. Eli Lilly is planning for Bydureon to be its only major product launch in the next three years.
Median A1C levels were similar among the groups, but hypoglycemia was more common in the premixed and bolus groups, and weight gain was more common in the bolus group. 28 The results of this study suggest that adding basal insulin to oral antihyperglycemics is similarly effective but has fewer adverse effects compared with adding premixed or bolus insulinThe goal of basal insulin is to suppress hepatic glucose production and improve fasting hyperglycemia (Figure 32). If basal insulin is titrated too high, it will also partially cover meals and lead to hypoglycemia during the night or if a meal is missed.
Long-acting analogue insulin may be administered once or twice daily, depending on the dose. The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Pharmacokinetic profile of using once-daily glargine, detemir, or NPH therapy.Adapted with permission from Diabetes Education Online. Short-acting analogue insulin is given up to 15 minutes before a meal to maintain two-hour postprandial glucose levels. Taking insulin after meals increases the risk of early postprandial hyperglycemia followed by delayed hypoglycemia.
Pharmacokinetic profile of using once-daily glargine, twice-daily detemir, or twice-daily NPH along with a short-acting analogue insulin before each meal.Adapted with permission from Diabetes Education Online. Replacement should be considered for patients with type 2 diabetes that is uncontrolled with augmentation therapy and who are able to comply with such a regimen or who desire tighter control. Bolus insulin should be added to basal insulin if fasting glucose goals are met but postprandial goals are not. When blood glucose levels are above predefined targets, additional short-acting insulin may be added to the bolus dose before meals. Fewer injections are needed, but patients are more restricted in their eating habits and schedule. Patients must eat breakfast, lunch, dinner, and possibly midmorning and bedtime snacks to prevent hypoglycemia.
Pharmacokinetic profile of using a short-acting analogue insulin or regular insulin along with NPH in a premixed insulin regimen.Adapted with permission from Diabetes Education Online.



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