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Diabetes Treatment

Medically reviewed on Apr 04, 2017 by L. Anderson, PharmD

Treatment of diabetes depends on which type of diabetes a patient has, either type 1 diabetes or type 2 diabetes.

  • Type 1 diabetes occurs when the body does not produce insulin, so replacement insulin must be delivered by injection, pump, or inhalation. People who have type 1 diabetes need to carefully plan and follow meals, timing of meals, and activity to keep their blood glucose (sugar) in check. It's important to measure blood sugar levels as low blood sugar can be dangerous, too.
  • Type 2 diabetes occurs when either the body makes too little insulin or the cells do not respond to insulin that is produced ("insulin resistance"). Patients with type 2 diabetes or prediabetes may be able to control their blood sugar levels by following a diet, exercise program and losing excess weight. If this first-line treatment does not control blood sugar levels effectively, an oral medication, often metformin first with other medications if needed, can be added to the treatment plan. Patients with type 2 diabetes may also need injected insulin, and in some circumstances it may be used as the first medication.

Patients and/or family members must learn to inject insulin if it is prescribed. In addition, patients with diabetes must learn to check and follow their blood sugar levels.

In addition to medications to control glucose, many patients with diabetes also need to take medicines to lower their blood pressure and cholesterol levels. When diet and exercise aren't satisfactory, weight loss medications such as Belviq, Contrave, Xenical, or Qsymia can also be used to help with the management of obesity. Statins, such as atorvastatin (Lipitor), rosuvastatin (Crestor), or pravastatin (Pravachol) are typically first-line prescription treatment for high cholesterol, also along with diet and exercise.

Learn MorePrescription Weight Loss / Diet Pills: What Are the Options?

Insulin

Injected insulin acts similar to endogenous insulin (insulin made by the body) to lower blood glucose levels.

There are several different types of insulin available in the United States. The various types of insulin differ in several ways:

  • in the source (animal, biosynthetic human, or genetically engineered)
  • in the time for the insulin to take effect
  • in the length of time the insulin remains working
  • in its dosage form (injected, inhaled).

Animal-sourced insulins (derived from the pancreas of cows and pigs) are no longer produced in the United States, but still may be available overseas.

The dose of insulin will be different for different patients, and patients may react differently to how quickly they respond to a dose. However, various types of insulin are available to help cover the mealtime and day-long needs for blood sugar control.

Common terms a patient might hear with regards to insulin use include:

  • Onset - how soon the insulin starts working.
  • Peak - when it is working most effectively.
  • Duration - how long the insulin lasts in the body.

Insulin is classified according to how it works in the body:

  • Rapid-acting: onset usually 10 to 30 minutes, with a peak at 30 minutes to 3 hours, and a duration up to 3 to 5 hours.
  • Short-acting: onset is usually 30 minutes to one hour, with a peak at 2 to 5 hours, and a duration up to 12 hours
  • Intermediate-acting: onset is usually 1.5 to 4 hours, with a peak at 4 to 12 hours, and a duration up to 24 hours.
  • Long-acting: onset usually 1 to 4 hours, with little to no peak, and a duration up to 24 hours.

What Are the Different Types of Insulin?

Rapid Acting Insulin

Brand Name Generic Name Onset Peak Duration
Apidra insulin glulisine 5 to 15 mins 45 to 75 mins 2 to 4 hours
Humalog insulin lispro 5 to 15 mins 45 to 75 mins 2 to 4 hours
NovoLog insulin aspart 5 to 15 mins 45 to 75 mins 2 to 4 hours

Short Acting - Insulin Regular (R) is also known as Soluble Insulin

Brand Name Generic Name Onset Peak Duration
Humulin R, Novolin R insulin regular (human) About 30 mins 2 to 4 hours 5 to 8 hours

Insulin regular used to be manufactured from beef and pork pancreas but is now available as human recombinant insulin. All brands of insulin from beef or pork origin have now been discontinued in the U.S.

Discontinued Brands of Insulin Regular

  • Regular Iletin II (insulin purified beef)
  • Iletin II, Regular Iletin II (Pork) (insulin purified pork)
  • Velosulin BR (insulin recombinant human)
  • Velosulin BR Human (insulin recombinant purified human)

Intermediate Acting Insulin

Brand Name Generic Name Onset Peak Duration
Humulin N, Novolin N insulin isophane (human, NPH) 1.5 to 2 hours 4 to 12 hours 18 to 28 hours

Discontinued Brands of Insulin Isophane

  • Insulated NPH Human (insulin suspension isophane semisynthetic purified human)
  • Insulin Insulated NPH Nordisk, NPH Iltein II (Pork) (insulin suspension isophane purified pork)
  • NPH Iletin I (Beef-Pork) (insulin suspension isophane beef/pork)
  • NPH Iletin II (insulin suspension isophane purified beef)
  • NPH Insulin (insulin suspension isophane beef

Discontinued Brands of Insulin Zinc

  • Humulin L, Novolin L (insulin zinc)
  • Lentard (insulin zinc Suspension Purified Beef/Pork)
  • Lente, Lente Iletin II (Pork) (insulin zinc suspension purified pork)
  • Lente Iletin II (insulin zinc suspension purified beef)
  • Lente Insulin (insulin zinc suspension beef)
  • Semilente (insulin zinc suspension prompt purified pork)
  • Semilente Insulin (insulin zinc suspension prompt beef)
  • Humulin U (insulin zinc extended)
  • Ultralente (insulin zinc suspension extended purified beef)
  • Ultralente Insulin (insulin zinc suspension extended beef)

Long Acting Insulin (Basal)

Long acting insulins are used to keep the blood sugar levels even throughout the day. Insulin glargine (Lantus, Basaglar) is a recombinant human insulin analog that is a man made form of the natural hormone. Due to its long duration of action it is injected just once a day.

Basaglar is a new biosimilar to Lantus approved in 2015. These insulins have the same active ingredients, but cannot be substituted for each other at the pharmacy without your doctor's approval. Basaglar may only save you a little at the pharmacy compared to Lantus, but check the manufacturers website for cost savings.

Insulin detemir and insulin degludec are also long-acting forms of insulin.

All long-acting insulins are dosed once per day.

Brand Name Generic Name Onset Peak Duration
Lantus, Basaglar insulin glargine 1 to 3 hours No peak 20 to 24+ hours
Levemir insulin detemir 1 to 3 hours 3 to 9 hours 6 to 24+ hours
Toujeo insulin glargine (Note: 300 units/mL)  6 hours No peak Up to 36 hours (steady state reached at ~5 days)
Tresiba insulin degludec 1 to 3 hours No peak 40+ hours (steady state reached in 3 to 4 days)

Inhaled Insulin

Afrezza (insulin human) Inhalation Powder was approved by the FDA in June 2014. Afrezza is an ultra rapid acting inhaled insulin indicated to improve blood sugar control in adult patients with diabetes. It is an insulin given through an inhaler at meals that helps to control blood sugar spikes due to mealtime insulin. It works by lowering levels of glucose (sugar) in the blood. It can be used in either type 1 or type 2 diabetes. In type 1 diabetes, it is given with injectable insulin.

Brand Name Generic Name Onset Peak Duration
Afrezza insulin inhalation 12 to 15 minutes About 1 hour About 2 to 3 hours

Exubera, also a rapid-acting inhaled insulin product, is no longer available on the US market. It was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal, although there may have been a possible association with an increased lung cancer risk.

Overall, success with inhaled insulins has been limited. This dosage form of insulin is not as effective as other treatments in helping patients to meet their blood sugar goal (A1C level less than 7 percent), and sales have been weak.

Premixed Insulin

Premixed insulin has two types of insulin mixed together in one vial. These are called biphasic insulins. This makes it easier to inject two different types of insulin at the same time.

The profile of the premixed insulin depends on the combination. Normally, one insulin will be rapid or short-acting and the other one has a longer duration of action.

Insulin lispro protamine and Insulin aspart protamine are suspensions of crystals produced from combining insulin lispro and protamine sulfate, and insulin aspart and protamine sulfate, respectively, under appropriate conditions for crystal formation. The addition of protamine makes insulin lispro and insulin aspart, which are rapid acting insulin, into intermediate acting insulin.

Brand Name Generic Name
Humalog Mix 50/50 insulin lispro/insulin lispro protamine
Humalog Mix 75/25 insulin lispro/insulin lispro protamine
Humulin 50/50 insulin isophane/insulin regular
Humulin 70/30 insulin isophane/insulin regular
Novolin 70/30 insulin isophane/insulin regular
Novolog Mix 70/30 insulin aspart/insulin aspart protamine
Ryzodeg 70/30 insulin aspart/insulin degludec

Discontinued Brands of Premixed Insulin

  • Insulin Nordisk Mixtard (Pork) (insulin purified pork/Insulin susp isophane purified pork)
  • Mixtard Human 70/30 (insulin recombinant purified human/Insulin suspension isophane semisynthetic purified human)

No generic or biosimilar forms of insulin are available on the U.S. market as of April 2017.

Oral Medicines to Treat Type 2 Diabetes

Oral medications are used in the treatment of type 2 diabetes, and may be the only treatment needed. Insulin is not always required in patients with type 2 diabetes, as it is with type 1 diabetes. These medications are used together with diet and exercise to treat type 2 diabetes.

The first line treatment for type 2 diabetes is usually diet and exercise and sometimes these measures alone are sufficient to bring blood glucose levels back to the normal range. If these measures do not effectively control blood glucose levels, one or a combination of oral medications may be necessary to control hyperglycemia.

Oral medications work by different mechanisms:

  • produce more insulin
  • decrease insulin requirements by the body
  • reduces gluconeogenesis (the formation of glucose from noncarbohydrates, such as protein or fat) by the liver 

Sulfonylureas

Sulfonylureas work by stimulating the pancreas to release more insulin and are only effective when there is some pancreatic beta-cell activity still present. These oral agents have been available for decades and are available in less expensive generic forms. Non-obese patients with type 2 diabetes are usually started on sulfonylureas.

Sulfonylureas are typically used if metformin alone does not adequately lower blood sugar; however, their effectiveness can decrease over time. Choice of sulfonylurea depends upon:

  • physician preferences
  • cost
  • pharmacy stock

A common side effect is hypoglycemia (low blood sugar); however, shorter-acting agents such as glipizide (Glucotrol) and glimepiride (Amaryl) may have less risk of hypoglycemia.This class may also cause weight gain and is therefore not suitable for obese patients. Sulfonyureas should not be used in patients with severe kidney disease. 

First Generation Sulfonylureas

Brand Name Generic Name
Diabinese chlorpropamide
Brands discontinued tolbutamide (available)
Brands discontinued tolazamide (available)

Second Generation Sulfonylureas

Brand Name Generic Name
Amaryl glimepiride
DiaBeta, Glynase Pres-Tab glyburide
Glucotrol, Glucotrol XL glipizide
Diamicron gliclazide (not commercially available in the U.S.)

Amaryl, Glynase, Glucotrol, and Glucotrol XL are available generically in the US an can save you hundreds of dollars per month.

Biguanides

Metformin is the only available biguanide; it is available in a cost-saving generic. In fact, metformin is the first drug of choice in most type 2 diabetic patients after a diagnosis.

It works by:

  • inhibiting the amount of glucose produced by the liver
  • increasing insulin-receptor binding
  • stimulating tissue uptake of glucose

Metformin does not stimulate the pancreas to make or release more insulin. It does not cause hypoglycemia or weight gain therefore obese patients with type 2 diabetes are usually started on biguanides.

Common side effects include abdominal discomfort, diarrhea, nausea or vomiting, loss of appetite, and metallic taste. Over time these side effects may lessen, and initial nausea may be relieved by taking metformin with food.

Brand Name Generic Name
Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet metformin

Alpha-Glucosidase Inhibitors

Alpha-Glucosidase inhibitors slow the digestion of carbohydrates and delay glucose absorption. They work by inhibiting intestinal enzymes that digest carbohydrates, thereby reducing carbohydrate digestion after a meal, which lowers postprandial (after a meal) blood sugar elevation in diabetics. They are not as effective as metformin or sulfonylureas at lowering blood glucose, but can be added to other treatments if needed.

Common side effects include:

  • abdominal pain
  • diarrhea
  • flatulence (gas)

which can worsen with higher doses. Start treatment with lower doses and titrate upwards to lessen adverse gastrointestinal side effects.

These drugs are taken three times daily at the start (with the first bite) of each main meal. As of April 2017, Precose is available in a cost-saving generic, but Glyset is not yet generically available.

Brand Name Generic Name
Glyset miglitol
Precose acarbose

Thiazolidinediones

Thiazolidinediones (also called glitazones) work by making the body's cells more sensitive to insulin, so less insulin is needed to move glucose from the blood into the cells. This leads to a reduction of blood glucose levels.

They should be taken in combination with other type 2 diabetes treatments such as metformin, a sulfonylurea, or insulin. Doses are usually given once daily and may be taken with or without food.

Common or serious side effects include: 

  • weight gain
  • swelling of feet, ankles
  • worsened heart disease (rare)
  • macular edema of the eye (rare)
  • cancer risk (rare)
  • bones fractures
Brand Name Generic Name
Actos pioglitazone
Avandia rosiglitazone

Meglitinides

Meglitinides are oral treatments that work by stimulating the pancreas to release insulin in response to a meal. They work similarly to sulfonylureas, but are safer to use in patients with kidney disease.

These agents are dosed 3 to 4 times a day, given before meals.

Hypoglycemia is a common side effect. Cough, runny or stuffy nose, sore throat are also more common side effects. If convulsions (seizures) or unconsciousness occur while taking repaglinide or nateglinide, call your health care provider immediately.

Brand Name Generic Name
Prandin repaglinide
Starlix nateglinide

Drug Combinations

Several drug combinations have become available to treat type 2 diabetes when additional blood sugar lowering is required.

These drugs might be given separately to a patient, so combining them into one tablet may help encourage patient compliance. However, the combination agents may be more costly and not available in a generic formulation.

In addition, it is often difficult to titrate doses to maximize blood glucose lowering when combination products are used. These medications may be best used when a patient has been established on a set dose of medication with minimal fluctuations in blood glucose.

Always check with your pharmacist to determine the most cost-effective treatment, and if generics are available.

Brand Name Generic Name
Actoplus Met, Actoplus Met XR metformin and pioglitazone
Avandamet metformin and rosglitazone
Avandaryl glimepiride and rosglitazone
Duetact glimepiride and pioglitazone
Glucovance glyburide and metformin
Janumet metformin and sitagliptin
Metaglip glipizide and metformin
Prandimet metformin and repaglinide
Kombiglyze XR metformin and saxagliptin
Jentadueto, Jentadueto XR linagliptin and metformin
Oseni alogliptin and pioglitazone
Kazano alogliptin and metformin
Invokamet, Invokamet XR canagliflozin and metformin
Xigduo XR dapagliflozin and metformin
Qtern dapagliflozin and saxagliptin
Glyxambi empagliflozin and linagliptin
Synjardy, Synjardy XR empagliflozin and metformin
Xultophy insulin degludec and liraglutide
Soliqua 100/33 insulin glargine and lixisenatide

Miscellaneous Antidiabetic Agents

Incretin Mimetics (GLP agonists)

The glucagon-like peptide (GLP) agonists, or incretin mimetics, are injectable agents that help the pancreas to produce insulin more efficiently. They bind to GLP-1 receptors and stimulate glucose dependent insulin release. These drugs inhibit glucagon secretion and slow gastric emptying. In turn, this prevents a steep rise in blood glucose levels after eating.

Clinically, they may be used:

  • as a third-line agent when oral medications are not fully successful in lowering blood sugar levels
  • in overweight type 2 diabetic patients who gain weight taking oral medication, as they can promote weight loss by suppressing appetite

Side effects include gastrointestinal problems like diarrhea, nausea, and rarely, pancreatitis. Contact a doctor right away if you have sudden and severe stomach pain. Patients with kidney impairment cannot use Byetta, Bydureon, or Adlyxin; the other agents should be used with caution. These drugs do not usually cause low blood sugar.

Dosing of incretin mimetics is by subcutaneous injection (into the fat layer between skin and muscle). As of April 2017, there were no generic alternatives available.

Brand Name Generic Name
Byetta, Bydureon exenatide
Victoza, Saxenda liraglutide
Tanzeum albiglutide
Trulicity dulaglutide
Adlyxin lixisenatide

Dipeptidyl Peptidase 4 (DPP-4) Inhibitors

DPP-4 inhibitors (often called "gliptins") are oral medications that work by regulating the levels of insulin the body produces after a meal. These drugs inhibit the enzyme dipeptidyl peptidase 4 which results in increased activity of incretins, which inhibits glucagon release.

The over effect of DPP-4 inhibitors is to:

  • increased insulin secretion from the pancreas in response to a meal
  • decrease gastric emptying
  • decrease blood sugar levels

This class of medication can be given with other oral agents when blood sugar levels are not at goal, as well in patients who cannot tolerate metformin or sulfonylureas; however, they are not usually used as first line treatments.

Side effects of DPP-4 inhibitors include diarrhea and stomach upset; however, they do not usually lead to hypoglycemia. Cost-saving generics are available for Nesina (alogliptin).

These medications are taken orally once a day with or without food.

Brand Name Generic Name
Onglyza saxagliptin
Januvia sitagliptin
Tradjenta linagliptin
Nesina alogliptin

Selective Sodium-Glucose Transporter-2 (SGLT-2) Inhibitors

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of oral antidiabetic drugs used in type 2 diabetes. SGLT-2 inhibitors work by lowering the renal (kidney) glucose threshold, resulting in an increased amount of glucose being excreted in the urine. These agents are not used first line for type 2 diabetes treatment, but can be combined with other medications. 

These agents will not lead to hypoglycemia (low blood sugar), but common side effects may include:

  • vaginal yeast infections
  • urinary tract infections
  • increased urination
  • thirst
  • stomach pain
  • male genital yeast infections.

These medications are usually taken by mouth once daily. Generic substitutions are not yet commercially available for any of these medicines.

Brand Name Generic Name
Invokana canagliflozin
Farxiga dapagliflozin
Jardiance empagliflozin

Amylin Analogs

Pramlintide (Symlin) is an injectable medicine for adults with type 1 and type 2 diabetes to control blood sugar. It works by three different mechanisms:

  • Slows down the rate that food moves from your stomach to your intestines, which help to keep your blood sugar levels from rising too quickly.
  • Lowers the amount of glucose (sugar) your liver produces.
  • After meals, triggers the feeling of fullness to control appetite and decrease food intake.

Pramlintide should only be used by people with type 1 or type 2 diabetes who already use their insulin as prescribed but still need better blood sugar control. Pramlintide is always used with insulin to help lower blood sugar during the 3 hours after meals.

Even when pramlintide is carefully added to mealtime insulin therapy, blood sugars may drop too low, especially in patients with type 1 diabetes. If this low blood sugar (severe hypoglycemia) happens, it is generally seen within 3 hours after a pramlintide injection.

Never mix pramlintide and insulin. You must use different syringes for pramlintide and insulin because insulin can affect pramlintide when the two are mixed together.

Brand Name Generic Name
Symlin pramlintide

Symptoms of Hypoglycemia (Low blood sugar)

Low blood sugar (hypoglycemia) due to medications is a symptom that people with both forms of diabetes may encounter. It is important to recognize the signs and symptoms of low blood sugar, which may include:

  • Sweating
  • Shakiness or nervousness
  • A feeling of hunger
  • Blurred vision
  • Anxiety
  • Confused

It's important to recognize the signs and symptoms of hypoglycemia early because untreated hypoglycemia can lead to:

  • Seizure
  • Unconsciousness
  • Death

To quickly treat low blood sugar, eat or drink 10 to 15 grams of a carbohydrate such as fruit juice, hard candy, or glucose tablets.

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