Types of Diabetes Type I And II Medications

Diabetic medications work in different ways to maintain normal blood glucose levels in people who have this metabolic autoimmune disorder.

Diabetes medications are prescribed for the management of diabetes, a metabolic disorder. Diabetic medications work in different ways to maintain normal blood glucose levels in diabetic patients.

Diabetes is a metabolic disease that causes high blood sugar levels (hyperglycemia), because the body does not properly convert food into energy. Food is normally converted into glucose, which is transformed into energy by the cells with the help of insulin. Insulin is a hormone produced by the pancreas.

Diabetic patients either lack insulin or have impaired functioning of insulin. Uncontrolled hyperglycemia over a long period can lead to serious health complications including blindness, kidney failure and heart disease. Types of diabetes include:

• Type I diabetes: Patients with type I diabetes produce little or no insulin at all due to genetic or other reasons. Type I diabetes was earlier known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. Type I occurs in up to 10% of diabetes diagnoses.
• Type II diabetes: Patients with type II diabetes may either be deficient in the level or the effective use of insulin. Type II diabetes is more common in adults and accounts for 90% of diabetes diagnoses. Risk factors include advanced age, obesity, family history, unhealthy eating habits and sedentary lifestyle.
• Gestational diabetes: Gestational diabetes develops during pregnancy in up to 5% of pregnancies, which can lead to a higher risk of developing diabetes later in life.

For nondiabetic adults, normal blood glucose level is within the range of 70 mg/dL to 99 mg/dL before eating (fasting) and below 140 mg/dL, two hours after eating (postprandial). The normal two to three-monthly glucose level average, known as HbA1c, is less than 5.7% in nondiabetic adults.

Blood glucose levels of 100-125 mg/dL fasting, 140-199 mg/dL postprandial and 5.7% to 6.4% Hb1Ac are considered prediabetes, and levels exceeding these values are considered to be diabetes.

For diabetic adults, the American Diabetes Association (ADA) recommends maintaining a fasting glucose level of 80 mg/dL to 130 mg/dL, postprandial level below 180 mg/dL, and a Hb1Ac of less than 7.0%.

There is no permanent cure for type II diabetes, however, it can be managed for a long term with weight loss, appropriate diet, exercise and medications. Some people may be able to reverse diabetes and manage normal blood sugar levels with diet and exercise, but diabetes does not get completely cured. There is no cure for type I diabetes, but it can be treated.

The primary treatment for type I diabetes is regular administration of insulin typically with injections in the tissue under the skin (subcutaneous). Other types of antidiabetic medications do not work, because type I diabetes patients lack the ability to produce any insulin.

Types of insulin

Human insulin is the only species of insulin currently available in the United States. Following are the types of insulin with approximate onset, peak and duration of effects, which depend on the dosage and also may vary from patient to patient:

Rapid-acting insulin

Onset is within 15 minutes with peak effect in 30 to 90 minutes and duration of effect up to four hours. Rapid-acting insulins include:

• Insulin aspart (NovoLog, Fiasp)
• Insulin lispro (Humalog)
• Insulin glulisine (Apidra)
• Insulin inhaled powder (Afrezza)

Short-acting insulin

Onset is in 30-60 minutes with peak effect in two to four hours and duration of effect up to eight hours. Short-acting insulins are known as bolus insulins, which act fast to bring down blood sugar spikes that come with meals.

• Insulin regular (Humulin R, Novolin R, Myxredlin)

Intermediate-acting

Onset is within one to two hours with peak effect in four to 10 hours, and duration of effects for 12-18 hours. A protein obtained from fish, known as neutral protamine Hagedorn (NPH or isophane insulin), is added to insulin to slow down its absorption and make the effects last longer. NPH also turns the insulin solution cloudy.

• Insulin NPH (Humulin N, Novolin N)

Long-acting

Onset of one to four hours with duration of effects lasting from 12 to 24 hours. The long- lasting insulins are known as basal insulins and provide a constant supply of insulin without any recognizable peak, to bring down high resting blood sugar level. 

• Insulin detemir (Levemir)
• Insulin glargine (Lantus, Basaglar, Toujeo)
• Insulin degludec (Tresiba) -- effects last up to 42 hours

Insulin combination products

Combination products are a mixture of rapid-acting and long-acting insulins, which have quick onset and long-lasting effect. Pre-mixed insulins are more commonly used for type II diabetes, as type I diabetes patients need frequent adjustments to their premeal insulin doses.

• Insulin aspart protamine/Insulin aspart
  • Novolog Mix 70/30
• Insulin lispro protamine/Insulin lispro
  • Humalog Mix 50/50
  • Humalog Mix 75/25
• Insulin NPH/Insulin regular
  • Humulin 70/30
  • Novolin 70/30
• Insulin degludec/insulin aspart
  • Ryzodeg 70/30

Insulin can be administered in several ways:

• Injections: Administered with needle and syringe.
• Insulin pen: A pen-like device with a needle to inject the insulin.
• Insulin pump: A device that maintains a continuous release of insulin through a thin tube implanted under the skin.
• Injection port: Injection is delivered through a thin tube that goes into the skin, which is replaced every week with a new one in a new spot.
• Jet injector: Delivers a fine spray of insulin at high pressure which is absorbed into the skin.
• Inhaler: A device to inhale the insulin in powder form.

Amylinomimetics

Amylin is a hormone produced by the pancreas, which is deficient in type I diabetic patients. Amylinomimetic is a synthetic analog of the human amylin, which reduces glucose level by:

• Delaying gastric emptying
• Suppressing release of glucagon, a hormone produced by pancreas, which raises glucose and fatty acids in the blood
• Modulating appetite

The FDA-approved amylinomimetic is:

• Pramlintide acetate (Symlin) injection

Hypoglycemia antidotes

When glucose level falls below the normal range (low range varies, discuss with your doctor; in general, it starts below 60-70 mg/dL) it is known as hypoglycemia, which is a major risk with diabetes treatment in both types of diabetes. Mild hypoglycemia may be treated by ingesting about a half cup of fruit juice or about 15 grams of carbohydrates like a tablespoon of sugar or honey. Hypoglycemia antidotes included for more severe low levels are:

• Glucagon hydrochloride (GlucaGen, Gvoke HypoPen)
• Glucagon intranasal (Baqsimi)

Medications and their dosages for type II diabetes are individualized based on the patient’s stage of diabetes and their response to the medication. Different medications work in different ways to maintain optimum blood glucose levels. Types of type II medications include:

• Biguanides
• Sulfonylureas
• Meglitinide derivatives
• Alpha-glucosidase inhibitors
• Thiazolidinediones (TZDs)
• Glucagonlike peptide–1 (GLP-1) agonists
• Dipeptidyl peptidase IV (DPP-4) inhibitors
• Selective sodium-glucose transporter–2 (SGLT-2) inhibitors
• Insulins
• Amylinomimetics
• Bile acid sequestrants
• Dopamine agonists

Biguanides

Biguanides reduce the glucose levels in three ways:

• Improve body’s response to natural insulin
• Reduce glucose absorption from the intestines
• Decrease glucose production by liver

The only biguanide currently available in the US is:

• Metformin hydrochloride (Fortamet, Glumetza)

Sulfonylureas

Sulfonylureas stimulate insulin production by the pancreas. Sulfonylureas include:

• Glimepiride (Amaryl)
• Glyburide (Diabeta, Glynase)
• Glipizide (Glucotrol, Glucotrol XL)
• Tolbutamide 

Meglitinides

Meglitinides also stimulate insulin production, but are short-acting and typically taken before a meal. Meglitinides include:

• Repaglinide
• Nateglinide

Alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors delay the absorption of carbohydrates and sugars, and prevent the sugar spike after a meal. Alpha-glucosidase inhibitors include:

• Miglitol (Glyset)
• Acarbose

Thiazolidinediones (TZDs)

Thiazolidinediones sensitize the body to respond better to insulin. It may be used as monotherapy if the patient’s pancreas produces sufficient insulin, or in combination with other medications. TZDs are the only type of antidiabetic medication which has been shown to be effective in slowing down the progression of diabetes, particularly in early stages of the disease.

TZDs include:

• Pioglitazone hydrochloride (Actos)
• Rosiglitazone maleate (Avandia)

Glucagonlike peptide–1 (GLP-1) agonists

Glucagonlike peptide–1 (GLP-1) agonists boost GLP-1 activity. (GLP-1) is a hormone known as incretin, which is secreted immediately after eating when glucose level rises. GLP-1 stimulates postprandial release of insulin, reduces glucagon and slows gastric emptying. GLP-1 agonists include:

• Exenatide synthetic (Byetta, Bydureon)
• Albiglutide (Tanzeum)
• Dulaglutide (Trulicity)
• Liraglutide recombinant (Victoza)
• Lixisenatide (Adlyxin)
• Semaglutide (Ozempic)
• Dipeptidyl peptidase IV (DPP-4) inhibitors

Dipeptidyl peptidase IV (DPP-4) inhibitors prolong the activity of incretins to stimulate release of insulin. DPP-4 is an enzyme produced in the body to degrade incretins such as GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). DPP-4 inhibitors include:

• Sitagliptin phosphate (Januvia)
• Saxagliptin hydrochloride (Onglyza)
• Linagliptin (Tradjenta)
• Alogliptin benzoate (Nesina)

Selective sodium-glucose transporter–2 (SGLT-2) inhibitors

Selective sodium-glucose transporter–2 (SGLT-2) inhibitors reduce glucose level by increasing its excretion in the urine. SGLT-2 inhibitors include:

• Canagliflozin (Invokana)
• Dapagliflozin (Farxiga)
• Empagliflozin (Jardiance)
• Ertugliflozin (Segluromet)

Bile acid sequestrants

Bile acid sequestrants were developed to lower cholesterol in the blood, but were also found to lower glucose. The effect, however, is not significant, and the way they work is unclear. Bile acid sequestrants may be prescribed as an adjunct therapy for diabetes, or to lower LDL cholesterol in people with prediabetes.

Bile acid sequestrants, as a rule, are not prescribed for high triglycerides, another kind of blood fat. The FDA-approved bile acid sequestrant as adjunct therapy for diabetes is:

• Colesevelam hydrochloride (Welchol)

Dopamine receptor agonists

Dopamine is a chemical (neurotransmitter) released by the hypothalamus in the brain. It is not clear how dopamine agonists work in reducing glucose, but when given in a single, timed morning dose, they appear to reduce the abnormal elevation in glucose and fatty acids, in insulin-resistant patients.

Dopamine agonists may be useful for obese patients who require minimal reduction of sugar levels and do not tolerate other diabetes medications. The FDA-approved dopamine agonist is a quick release formulation of:

• Bromocriptine mesylate (Cycloset)

Amylinomimetics

Amylinomimetics are synthetic analogs of the human amylin, a hormone secreted by pancreas, which lowers glucose. Other than insulin, amylinomimetics are the only antidiabetic medication prescribed for type I diabetes also. The only available amylinomimetic in the US is:

• Pramlintide acetate (Symlin) injection

Insulins

While insulin is the mainstay treatment for type I diabetes, it is used for treating type II diabetes when the glucose levels cannot be managed with diet, weight loss, exercise and oral medications. For some people insulin therapy may be used for a short period to bring down acute elevation in glucose levels.

Most type II diabetes patients ultimately become insulin-deficient with the progression of disease, and will require insulin therapy. Many type II diabetes patients also develop insulin resistance, so insulin therapy is individualized based on each patient’s condition.

Combination medications

Combination medications available for type II diabetes include:

• Glyburide/metformin
• Glipizide/metformin (Metaglip)
• Pioglitazone/metformin (Actoplus Met, Actoplus XR)
• Pioglitazone/glimepiride (Duetact)
• Alogliptin/metformin (Kazano)
• Alogliptin/pioglitazone ((Oseni)
• Canagliflozin/metformin (Invokamet)
• Dapagliflozin/metformin (Xigduo XR)
• Sitagliptin/metformin (Janumet, Janumet XR)
• Saxagliptin/metformin (Kombiglyze, Kombiglyze XR)
• Linagliptin/metformin (Jentadueto)