By Kim Ladd, RN,BS,CPHQ,CDCES, October 2021

Why Diabetes Medications?

The cornerstone of diabetes management is keeping blood sugar levels under control (80 -130 mg/dcl) to help prevent complications of diabetes.

In addition to healthy eating, stress management and physical activity, diabetes medications are another way to help manage blood sugar levels.

If you have type 1 diabetes, your body no longer produces the hormone insulin to control your blood sugar levels, so you must take insulin either by injections, inhalation, an insulin pump, or a system like the OmniPod.

If you have type 2 diabetes and require medications to help control your blood sugar levels then there are many options, from oral medications to injections.

Classifications of Oral Medications for Type 2 Diabetes

  • Biguanides
  • Sulfonylureas
  • SGLT 2 Inhibitors
  • DPP-4 Inhibitors
  • Thiazolidinediones “TZDs”
  • Glucosidase Inhibitors
  • Meglitinides
  • Dopamine Receptor Agonists
  • Bile Acid Sequestrants
  • GLP-1 Receptor Agonist (GLP-1 RA)

BIGUANIDES decrease hepatic (liver) glucose output. Biguanides tell your liver to hang on to some of the glucose it makes.                                                                           

  • metformin (Glucophage)                                            
  • Riomet (liquid metformin)                                                        
  • Glucophage XR (extended release)                                 
  • Glumetza (extended release)                                                     
  • Fortamet          (extended release)                                           

Biguanides are the first-line medication for the treatment of type 2 diabetes. More than 150 million people worldwide use metformin and it is the 4th most prescribed drug in the United States.

Side effects: nausea, bloating, diarrhea, B12 deficiency. To help minimize the gastrointestinal side effects, take with meals and/ or switch to the extended release form. If you experience any of the following symptoms, stop taking metformin and call your doctor immediately: extreme tiredness, weakness, or discomfort, stomach pain, decreased appetite; deep and rapid breathing or shortness of breath, dizziness, lightheadedness, fast or slow heartbeat, flushing of the skin, muscle pain, or feeling cold, especially in your hands or feet.

Benefits: lowers cholesterol, no hypoglycemia or weight gain, cheap. Approved for use in ages 10 years and older. Lowers A1c 1.0%-2.0%.

SULFONYLUREAS increase the release of insulin from the pancreas; they “tell” your pancreas to make more insulin. They are effective only when a person still has some residual pancreatic beta cells.                    

  • glyburide (Diabeta)                                                                      
  • glipizide (Glucotrol)         
  • glimepiride (Amaryl)

Sulfonylureas were the first oral medications developed to treat diabetes; developed in the 1940s. As a result, they are a very low-cost medication.

Side Effects: hypoglycemia and weight gain. Avoid skipping meals because this medication causes your beta cells to produce insulin all day long. If you skip meals, your blood glucose level may go too low (hypoglycemia). You need to stick with a meal schedule, and eat even if you are not hungry, to ensure that the insulin has enough glucose to process throughout the day.

Caution: Glyburide is most likely to cause hypoglycemia especially in alcohol abusers or if you are malnourished

Benefits: Lowers A1c 1.0% – 2.0%

SGLT2 INHIBITORS decrease glucose reabsorption in kidneys. They are commonly known as “glucoretics” because they work by making your kidneys pee out extra sugar.                                                                                    

  • canagliflozin (Invokana)
  • dapagliflozin (Farxiga)
  • empagliflozin (Jardiance)
  • ertugliflozin (Steglatro)

Side effects: hypotension (low blood pressure), UTIs (urinary tract infections), increased urination, genital infections, ketoacidosis. Canagliflozin increases risk of amputation.

Benefits:  Reduce risk of cardiovascular death, heart failure and preserve long-term kidney function, no hypoglycemia or weight gain. Lowers weight 1-3 lbs. Lowers A1c 0.6%-1.5%.

DPP-4 INHIBITORS are also known as“incretin enhancers”. They prolong the action of gut hormones; increase insulin secretion; and delay gastric emptying. They work by blocking the action of DPP-4, an enzyme that destroys a group of gastrointestinal hormones called incretins. Incretins help stimulate the production of insulin when it is needed (such as after eating) and reduce the production of glucagon (sugar) by the liver when it is not needed (such as during digestion).       

  • sitagliptin (Januvia)
  • saxagliptin (Onglyza)
  • linagliptin (Tradjenta)
  • alogliptin (Nesina)

Side effects: headache and flu-like symptoms. Can cause severe, disabling joint pain. Report signs of pancreatitis. Saxagliptin and alogliptin can increase risk of heart failure. Notify your physician if you have shortness of breath, edema, or weakness.

Benefits: No weight gain or hypoglycemia. Lowers A1c 0.6%-0.8%.

THIAZOLIDINEDIONES “TZDs” are also known as glitazones.TZDs increase insulin sensitivity by reducing circulating fatty acid concentrations and lipid availability in the liver and muscles. They help insulin work better and help lower insulin resistance from your cells so your pancreas doesn’t have to work as hard.

  • pioglitazone (Actos)
  • rosiglitazone (Avandia)

Side effects: edema (fluid buildup), weight gain, macular edema and heart failure. Black Box Warning: TZDs may cause or worsen CHF (congestive heart failure), so monitor for edema and weight gain. They may also increases a person’s peripheral fracture risk. Actos may increase risk of bladder cancer.

Benefits: Lowers A1c 0.5% – 1.0%

GLUCOSIDASE INHIBITORS delay the absorption of carbohydrates from the small intestine, which has a lowering effect on postprandial (after meals) blood glucose and insulin levels. They slow the digestion of food with complex carbohydrates (ex: bread, pasta, rice, potatoes, corn) which keeps your blood sugar from shooting up after you eat.                                                         

  • acarbose (Precose)
  • miglitol (Glyset)

Side effects: hypoglycemia, gastrointestinal (gas, diarrhea, bloating, and abdominal cramps). To help decrease these side effects, start medicine at a low dose and slowly increase at 4-8 week intervals. 

Benefits: Lowers A1c 0.5%– 1.0%.

MEGLITINIDES “tell” your pancreas to make more insulin. Because they work by stimulating insulin secretion, they are useful only in patients with some pancreatic beta cell function.

  • repaglinide (Prandin)
  • nateglinide (Starlix)

Side effects: hypoglycemia and weight gain. To avoid hypoglycemia take before meals and do not take pill then skip a meal.

Benefits: Lowers A1c 1.0% – 2.0%.

DOPAMINE RECEPTOR AGONISTS reset your body’scircadian rhythm. This medication works directly on the brain to help it process dopamine. This, in turn, can increase your sensitivity to insulin so your body doesn’t need as much of it. You also need to implement some lifestyle changes such as a healthy diet and exercise for the medication to be more effective. 

  • bromocriptine mesylate (Cycloset)

Side effects: nausea, vomiting, dizziness, drowsiness, lightheadedness, tiredness, constipation, or headache.

Take medicine within 2 hours of waking.

Benefits: Lowers A1c 0.6% – 0.9%.

BILE ACID SEQUESTRANTS decrease cholesterol and blood glucose levels. They belong to a class of drugs called bile acid-binding resins. Bile acid is a natural substance the liver makes by using cholesterol. This medication works by removing bile acid from the body which causes the liver to make more bile acid by using cholesterol, which reduces cholesterol levels in the blood. It is not known how colesevelam works in lowering blood sugar levels.                                             

  • colesevelam HCL (Welchol)

Side effects are gastrointestinal in nature. Do not use if you have a history of bowel obstruction, triglycerides >500, or pancreatitis. Can decrease the absorption of certain medications such as glipizide and soluble vitamins.

Benefits: Lowers LDL cholesterol by 15%-30%. Lowers A1c ~ 0.5%

Combination Oral Medications

  • Trijardy XR = empagliflozin, linagliptin, metformin XR
  • ACTOplus Met = pioglitazone, metformin; also in XR form
  • Duetact = pioglitazone, glimepiride
  • Glucovance = glyburide, metformin
  • Glyxambi = empagliflozin, linagliptin
  • Invokamet = canagliflozin, metformin
  • Janumet = sitagliptin, metformin; also in XR form
  • Jentadueto = linagliptin, metformin
  • Kazano = alogliptin, metformin
  • Kombliglize XR = Onglyza, metformin XR
  • Metaglip = glipizide, metformin
  • Oseni = alogliptin, pioglitazone
  • Prandimet = repaglinide, metformin
  • Qtern = saxagliptin, dapagliflozin
  • Segluromet = ertugliflozin, metformin
  • Steglujan = ertugliflozin, sitagliptin
  • Synjardy = empagliflozin, metformin; also in XR form
  • Xigduo XR = dapagliflozin, metformin

GLP-1 Receptor Agonist (GLP-1 RA) is a new oral medication class for type 2 diabetes. They are also known as “incretin mimetics” and they increase insulin release with food, slow gastric emptying, promote satiety (feeling of fullness) and suppress glucagon.

  • semaglutide (Rybelsus)

Take pill on an empty stomach when you first wake up with a sip of plain water; after 30 minutes, you can eat, drink, or take other oral medicines

Side effects: nausea, stomach abdominal pain, diarrhea, decreased appetite, vomiting, and constipation. Severe side effects: hypoglycemia, pancreatitis, vision changes, kidney problems.

Benefits: Weight loss of 1.6 to 6.0kg (3.5 to 13 pounds). Lowers A1c 0.5 % – 1.6%

INSULIN

Insulin is a hormone made by the pancreas and it’s main function is to regulate glucose (sugar) metabolism by moving glucose out of the bloodstream and into cells where it can be used for energy. Insulin directly lowers glucose levels by increasing glucose uptake into muscle and fatty tissue, and reducing the release of glucose from the liver.

If you have type 1 diabetes, you will be taking insulin because your pancreas has lost the ability to produce insulin. If you have type 2 diabetes and your pancreas cannot produce enough insulin and other medications cannot regulate your blood sugar levels properly, then it may be time for insulin.

Insulin doses are drawn up from a vial using a syringe, administered by an insulin pen, inhaled through the throat, or delivered through an insulin pump, depending on the type of insulin. Insulin pens are the most accessible option for people with low or no vision.

When administering insulin, you inject it into subcutaneous tissue (subq, aka fatty tissue) on your abdomen, legs, back of arms, or buttocks. It is important to rotate injections sites to prevent the formation of scar tissue.

Insulin can’t be taken in pill form because your digestive system would break it down in the same way that you digest food. That means the insulin wouldn’t make it to your bloodstream where it’s needed.

Insulins Classifications for Type 1 and Type 2 Diabetes

  • Rapid Acting
  • Short Acting
  • Intermediate Acting
  • Long Acting
  • Intermediate + Short
  • Intermediate + Rapid
  • Concentrated
  • Inhaled

Insulins are either a bolus or a basal insulin.

  • Bolus insulin lowers after-meal glucose. Post-meal blood glucose levels reflect efficacy.
  • Basal insulin controls blood glucose levels between meals and nighttime. Fasting blood glucose levels reflect efficacy.

Insulin side effects: hypoglycemia, weight gain, lipodystrophy (skin lesions at injection sites; rotate injection sites to decrease). 

Typical dosing range: 0.5-1.0 units/ kg body wt/day.

Discard open insulin vials after 28 days. For pen storage guidelines, see package insert.

The American Diabetes Association characterizes insulin by the way it works.

  • Onset: the length of time it takes insulin to enter your bloodstream and begin to lower blood glucose levels.
  • Peak: the time during which insulin is at its “peak” or maximum effectiveness at lowering blood glucose levels.
  • Duration: the length of time insulin continues to lower blood glucose levels.

Rapid Acting Insulins are BOLUS insulins thatbegin to lower your blood sugar levels within 1 to 15 minutes (onset).

                                                                    Onset:                  Peak:                    Duration:  

  • aspart (Fiasp)                                  2 ½ mins              60 mins                3-5 hours
  • Lispro-aabc (Lyumjev)                      1 min                   60 mins                4-5 hours  
  • aspart (Novolog)                             5-15 mins            30-90 mins          <5 hours   
  • lispro (Humalog, Admelog)            5-15 mins            30-90 mins          <5 hours   
  • glulisine (Apidra)                             5-15 mins            30-90 mins          <5 hours   

Rapid acting insulins are prescribed as either a fixed dose or as a sliding scale dose (based on your blood sugar level or as a carb counting ratio).

Insulin pumps use rapid-acting insulins.

Short Acting Insulins are BOLUS insulins that begin to lower your blood sugar levels within 30 to 60 minutes (onset). They are also known as ‘regular’ insulin.

Onset:                    Peak:                    Duration:                             

  • Humulin R           30-60 mins                    2-3 hours                   5-8 hours
  • Novolin R             30-60 mins                   2-3 hours                   5-8 hours
  • ReliOn R              30-60 mins                   2-3 hours                   5-8 hours
  • Iletin R                 30-60 mins                   2-3 hours                   5-8 hours

Short acting insulins are prescribed as either a fixed dose or as a sliding scale dose (based on your blood sugar level or as a carb counting ratio).

Regular insulin was the 1st insulin developed, in 1921. It was first given to patients in 1922. As a result, they are one of the most inexpensive insulins. ReliOn R insulin is available at Walmart pharmacy for $25/vial without a prescription.

Intermediate Acting Insulins are BASAL insulins that begin to lower your blood sugar levels within 2 to 4 hours (onset). They are also known as ‘NPH’ insulin.

Onset: Peak: Duration:

  • Humulin N                    2-4 hours             4-10 hours           10-16 hours
  • Novolin N                      2-4 hours             4-10 hours           10-16 hours
  • ReliOn N                        2-4 hours             4-10 hours           10-16 hours
  • Iletin N                          2-4 hours             4-10 hours           10-16 hours

Intermediate acting insulins are prescribed as a fixed dose.

NPH was the 2nd insulin developed, in 1946. As a result, they are one of the most inexpensive insulins. ReliOn N insulin is available at Walmart pharmacy for $25/vial without a prescription.

Long Acting Insulins are BASAL insulins that begin to lower your blood sugar levels within 1 to 8 hours (onset).                                

Onset: Peak: Duration:

  • detemir (Levemir)                      3-8 hours             none           6-24 hours
  • glargine (Lantus, Basaglar)             2-4 hours             none           20-24 hours        
  • degludec (Tresiba)                        ~ 1 hour               none           <42 hours           

Long acting insulins are prescribed as a fixed dose. You administer them 1 x/day at the same time every day.

Combo Intermediate + Short Acting Insulins are a combination of NPH and Regular insulins. They are both a BOLUS and a BASAL insulin that begin to lower your blood sugar levels within 30 to 60 minutes (onset).          

                                                         Onset:                  Peak:                    Duration:

70/30 = 70% NPH + 30% Reg    30-60 mins          dual peaks           10-16 hours       

50/50 = 50% NPH + 50% Reg    30-60 mins          dual peaks           10-16 hours                                    

If you have to mix your dose yourself (using regular insulin from a vial and NPH insulin from a vial), you draw up the regular insulin (clear) into syringe first; then draw up the NPH (cloudy) into same syringe, so that only one injection is needed.

Combination intermediate and short acting insulins are prescribed as a fixed dose; you administer them 1 or 2 x/day at the same time every day.

Combo Intermediate + Rapid Insulins are both a BOLUS and a BASAL insulin that begin to lower your blood sugar levels within 5 to 15 minutes (onset).                                                                                              Onset:                  Peak:                    Duration:

  • Novolog Mix 70/30                             5-15 mins            dual peaks           24 hours (70 % insulin aspart protamine/ 30% insulin aspart)
  • Humalog Mix 75/25                             5-15 mins              dual peaks           24 hours
  • Humalog Mix 50/50                             5-15 mins              dual peaks           24 hours (% insulin lispro protamine/ % insulin lispro)

Combination intermediate and rapid acting insulins are prescribed as a fixed dose; you administer them 1 or 2 x/day at the same time every day.

Concentrated Insulins were developed to help decrease the amount of insulin needed in an injection.

Rapid Acting High Dose Insulins are BOLUS insulins that are 2 times the concentration of u-100 insulin and have 200 units of insulin/ml.

Onset: Peak: Duration:

  • U-200 insulin lispro (Humalog U200)         10-15 mins 1-3 hrs          3-5 hrs      

They come dispensed in a 3ml Kwik Pen, are prescribed as a fixed dose, sliding scale or carb counting ratio and administered prior to each meal.               

Ultra Long Lasting Insulins are BASAL insulins that are 2 times the concentration of u-100 insulin and have 200 units of insulin/ml.                             

  Onset: Peak: Duration:

  • insulin degludec U-200 (Tresiba U200)            1 hr          no peak          up to 42 hrs   
  • insulin degludec (IDEG U200)                     1 hr          no peak          up to 42 hrs

Ultra long lasting insulins are prescribed as a fixed dose; you administer it 1 x/day at the same time every day.                                                                                                                             

Ultra Basal insulin is a BASAL insulin that is 3 times the concentration of u-100 insulin and has 300 units of insulin/ml.                                                 

Onset: Peak:     Duration:

  • insulin glargine U-300 (Toujeo Solostar)    6 hrs           none     up to 36 hrs   

It is prescribed as a fixed dose; you administer it 1 x/day at the same time every day.

Short Acting High Dose is a regular insulin that is a BOLUS insulin used as a BASAL insulin. It is 5 times the concentration of u-100 insulin (500 units insulin/mL) and is used in people taking 200+ units of insulin daily.         

Onset: Peak: Duration:

  • Humulin Regular U-500                   15- 30 min           4-8 hrs          13-24 hrs

Only use U-500 insulin with the designated U-500 insulin syringe (has a green cap).

It is prescribed as a fixed dose; you administer it 2 to 3 x/day, 30 minutes before a meal.

Inhaled Insulin is regular insulin administered through your throat by inhalation. It is 2 times the concentration of U-100 insulin.After you inhale Afrezza (insulin), the insulin passes quickly through your lungs and into your bloodstream, where it begins lowering your blood sugar level.                                             

                                                          Onset:                  Peak:                    Duration:

  • Afrezza Inhaled                     ~12 mins           35-45 mins 1.5- 3 hours

The medicine comes in cartridges of 4, 8, or 12 unit cartridges. You inhale this insulin as ordered, before meals. The side effects of Afrezza include hypoglycemia, throat irritation, cough and bronchospasm. Avoid this medicine if you have lung disease.

Find out about how to administer Afrezza inhaled insulin.

Injectable Medications for Type 2 Diabetes

GLP-1 Receptor Agonist (GLP-1 RA) are injectable medication to help control type 2 diabetes. They are NOT insulin. GLP-1 RA medications are also known as “incretin mimetics” and they increase insulin release with food, slow gastric emptying, promote satiety (feeling of fullness) and suppress glucagon.                     

  • exenatide (Byetta)                         Inject 2 x a day
  • exenatide XR (Bydureon)                   Inject 1 x a week
  • liraglutide (Victoza)                        Inject 1 x a day
  • dulaglutide (Trulicity)                      Inject 1 x a week
  • lixisenatide (Adlyxin)                       Inject 1 x a day
  • semaglutide (Ozempic)            Inject 1 x a week

Side effects for all: nausea, vomiting, weight loss, injection site reaction. Pay attention to any signs of pancreatitis (severe abdominal pain, vomiting) and report them to your physician immediately. Black box warning: Thyroid C-cell tumor warning for exenatide XR, liraglutide, dulaglutide, and semaglutide (avoid if family history of medullary thyroid tumor). 

Benefits: Victoza and Ozempic significantly reduce risk of CV death, heart attack, and stroke. Bydureon and Victoza approved for use in children 10 years old and over. Weight loss of 1.6 to 6.0kg (3.5 to 13 pounds) and lowers A1c 0.5% – 1.6%.

Insulin/Injectable Combo Medications for Type 2 Diabetes

  • iDegLira (Xultophy 100/3.6)

Combines: insulin degludec (IDeg or Tresiba): ultra long insulin + liraglutide (Victoza): GLP-1 Receptor Agonist. It is a once daily injection and is supplied in 3ml pens.

  • iGlarLixi (Soliqua 100/33)

Combines: insulin glargine (Lantus): basal Insulin + lixisenatide (Adlyxin): GLP-1 ReceptorAgonist. Inject this medicine once a day an hour prior to first meal of the day. It is supplies in 3ml pens.

Injectable Medication for Type 1 and Type 2 diabetes

Amylin Mimetic slows gastric emptying and suppresses the release of glucagon. It is sometimes used in people with type 1 and type diabetes that take insulin.

  • pramlintide (Symlin)

Take this medication immediately before major meals.

Side effects: severe hypoglycemic risk so decrease insulin dose when starting, nausea, weight loss.

Benefits: lowers A1c 0.5% – 1%

As a person living with diabetes, it is important to understand the different types of medications used to help control blood sugar levels. Being informed about your medications makes it easier and safer to take them properly, to have a conversation with your diabetes health care team, and to be an active member in the decision-making of your diabetes management plan.

Resources

Medication & Treatments: Get a handle on diabetes medication. The more you know, the better you’ll feel. From the American Diabetes Association

Oral Diabetes Medications from the Cleveland Clinic.

Diabetes Medicines by Medline Plus

Insulin, Medicines, & Other Diabetes Treatments from the National Institutes of Health

Diabetes Guides in English and Spanish with Lessons Following Seven Self-Care Behaviors – VisionAware