Titration is targeted at fasting plasma glucose (FPG). • Released at Lantus. Glargine U/ml. Toujeo. Glargine U/ml. Tresiba. Degludec. Novolog 70/30 . (*Inform patient to hold titration until further evaluation if develops any . Start NPH before bed at 40% of total daily Lantus/Levemir dose* (then titrate per basal . Basal Insulin Therapy and Basal Insulin Titration Algorithms for T2DM: What Is of insulin glargine—following a specific titration algorithm—added to metformin.

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A more recent article on type 2 diabetes mellitus is available. Insulin therapy may be initiated as augmentation, starting at 0.

When using replacement therapy, 50 percent of titratioh total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Augmentation therapy can include basal or bolus insulin. Replacement therapy includes basal-bolus insulin and correction or premixed insulin. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered titratikn choosing therapy.

Metformin should be continued if possible because it is proven to reduce all-cause mortality and cardiovascular events in overweight patients with diabetes. 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. Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications.

Insulin is secreted continuously by beta cells in a glucose-dependent manner throughout the day. It is also secreted in response to oral carbohydrate loads, including a large first-phase insulin release that suppresses hepatic glucose production followed by a slower second-phase insulin release that covers ingested carbohydrates 1 Figure 1 2.

Analogue insulin is as effective as human insulin but is associated with less postprandial hyperglycemia and delayed hypoglycemia. Fasting glucose readings should be used to titrate basal insulin, whereas both preprandial and postprandial glucose readings should be used to titrate mealtime insulin. Metformin Glucophage combined with insulin is associated with decreased weight gain, a lower insulin dose, and less hypoglycemia compared lantys insulin alone.

Oral medications should not be abruptly discontinued when starting insulin therapy because of ritration risk of rebound hyperglycemia.

For information about the SORT evidence rating system, go to https: Insulin is secreted by the pancreas in a glucose-dependent manner continuously tihration the day, as well as in response to oral carbohydrate loads. Adapted with permission from Diabetes Education Online. University of California, San Francisco. Accessed December 10, Type 2 diabetes mellitus is associated with insulin resistance and slowly progressive beta-cell failure.

By the time type 2 diabetes is diagnosed in patients, up to one-half of their beta cells are not functioning properly.

Pain, weight gain, and hypoglycemia may occur with insulin therapy. Pain is associated with injection therapy and glucose monitoring, although thinner and shorter needles are now available to help decrease pain. 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.

Prospective Diabetes Study, patients with type 2 diabetes who were taking insulin gained an average of 8 lb, 13 oz 4 kgwhich was associated with a 0.

Hypoglycemia may occur from a mismatch between insulin and carbohydrate intake, exercise, or alcohol consumption. Hypoglycemia titrattion been associated with an increased risk of dementia and may have implications in cardiac arrhythmia. 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.

The blood glucose level should be rechecked after 15 minutes to make sure it has normalized.


Insulin Management of Type 2 Diabetes Mellitus

An epidemiologic study has raised concern about cancer risk with glargine Lantus and other insulin therapies. A consensus statement by the ADA indicates that this possible risk needs further research but should not be a limiting factor in treatment choice. The American College of Endocrinology and the American Association of Clinical Endocrinologists recommend initiation of insulin therapy in patients with type 2 diabetes and an initial A1C level greater than 9 percent, or if the diabetes is uncontrolled despite optimal oral glycemic therapy.

This recommendation is based on expert opinion, and not on the results of randomized controlled trials comparing different approaches in patients with an initial A1C level greater than 9 percent.

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. Recent trials have shown that intensive glucose control i. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing a type of insulin.

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. An industry-funded cost-effectiveness analysis found that the increased cost of medication is more than off set by the reduction in hypoglycemic events.

Common Standards of Basal Insulin Titration in T2DM

Insulin regimens should be tailored to the patient’s needs and lifestyle. Table 2 defines commonly used terms in insulin therapy. Adapted with permission from Endotext. Insulin pharmacology, types of regimens and adjustments.

Accessed December 6, Adapted from Hirsch IB. N Engl J Med. Use of either basal or bolus insulin to help improve glucose control in patients with partial beta-cell failure.

Use of basal and bolus insulin to control blood glucose when endogenous insulin production is minimal or absent. The number of units of insulin pantus to cover for a certain number of grams of carbohydrates ingested.

How much 1 unit of insulin is expected to decrease the patient’s blood glucose level; when the blood glucose level is above predefined targets, short-acting insulin may be added to the bolus dose or given separately between meals. In one study, patients who had uncontrolled type 2 diabetes and were taking a sulfonylurea and metformin were randomized to receive premixed, bolus, or basal analogue insulin. 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.

The goal of basal insulin is to suppress hepatic glucose production and improve fasting hyperglycemia Figure 3 2. 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.

Lower doses may not last 24 hours, whereas higher doses may impede insulin absorption. NPH may be administered one to three times daily.

NPH is often used during pregnancy and in patients who are unable to afford the up-front cost of analogue insulin. Augmentation therapy with basal insulin. Pharmacokinetic profile of using tihration glargine, detemir, or NPH therapy. Bolus insulin may also be used for augmentation Figure 4 2. Short-acting insulin is administered before meals to cover the carbohydrate load. Short-acting llantus 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. Replacement therapy with basal-bolus insulin. Pharmacokinetic profile of using once-daily glargine, twice-daily detemir, or twice-daily NPH along with a short-acting analogue insulin before each meal.


Replacement therapy includes basal-bolus insulin and correction or premixed insulin; an insulin pump may be used, but is beyond the scope of this article. 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.

For example, a patient takes 40 units of glargine daily and 12 units of lispro Humalog before each meal, and has a correction factor of 1 unit for every 20 mg per dL 1. If the blood glucose level at breakfast is mg per dL 8. Premixed insulin similarly reduces A1C compared with basal-bolus insulin. 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.

If used, correction insulin must be administered separately with a short-acting insulin. This may increase the number of injections compared with basal-bolus therapy Figure 5 2.

Pharmacokinetic profile of using a short-acting analogue insulin or regular insulin along with NPH in a premixed insulin regimen. The initial dosage of insulin is individualized based on the patient’s insulin sensitivity. Insulin therapy may be started with a set dosage, such as 10 units of glargine daily, or by using weight-based equations. Equations to estimate augmentation, replacement, carbohydrate ratio, and correction therapy are listed in Table 2.

When using replacement therapy, 50 percent of the lxntus daily insulin dose is given as basal and 50 percent as bolus, divided up before breakfast, lunch, and dinner. For example, a kg lb patient requiring basal-bolus and correction insulin would need 36 units of basal insulin 0. Some physicians have adopted the Treat-to-Target Trial’s titration schedule for basal insulin Table 4.

Recent studies have found no lanntus benefit with A1C targets of 6. Some microvascular benefit has been associated with A1C targets of 6. Adapted with permission from American Diabetes Association. Standards of medical ttitration in diabetes— [published correction appears in Diabetes Care. Patients should go to the physician’s office for follow-up at least every three to four months.

The frequency of communicating insulin titration via clinical contact, telephone, e-mail, or fax is highly correlated with improvement of A1C levels. Insulin is effective only if administered appropriately.

The needle should be placed at a degree angle to the skin and held in place for five to 10 seconds after injection to prevent insulin leakage. Rotation of injection sites is important to prevent lipohypertrophy i. Insulin is available in titratoin and vials. 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.

Patients should be instructed to prime the insulin pen before every use. Priming consists of drawing up 1 or 2 units of insulin and injecting into the air to allow the insulin to fill the needle. Many oral medications are safe and effective when combined with insulin therapy. To maximize benefit without causing significant adverse effects, it is important to consider the mechanism lahtus action for different therapies.