When is medication considered?

Whether or not blood-sugar-lowering medication is suitable will depend on things like the age at which type 2 diabetes starts. Many older people with type 2 diabetes have slightly higher blood sugar levels than normal and they don’t cause any problems. When type 2 diabetes develops in older age, it rarely leads to nerve and blood vessel damage. Other conditions like high blood pressure are often more of a problem then.

If you’re already diagnosed with type 2 diabetes around the age of 40 or 50, you will probably live with the condition for quite a long time. Then even slightly too high blood sugar levels can lead to other problems over a long period of time. So it's very important for younger people who have type 2 diabetes to keep their blood sugar levels down.

The aim of the treatment is to prevent the diabetes from leading to other health problems. Constantly high blood sugar levels can cause damage to blood vessels and nerves. This can result in medical problems affecting the kidneys, feet and retina (the lining of the back of the eye). The risk of stroke or heart attack may also increase. Blood-sugar-lowering drugs are used with the aim of preventing or delaying these health problems as much as possible.

What other medications lower the risk of cardiovascular disease?

Type 2 diabetes increases the risk of cardiovascular (heart and blood vessel) disease. People with type 2 diabetes often have other risk factors as well, like high blood pressure. It is then quite likely that treating those other factors with medication will lower the risk of a heart attack or stroke more effectively than keeping blood sugar levels down. The main types of medication are:

• Blood-pressure-lowering drugs (antihypertensives)
• Low doses of acetylsalicylic acid (the drug in medicines like "Aspirin") for preventing blood clots
• Statins for lowering cholesterol levels

All of these medications can have side effects and also interact with other medications. So it's important to talk to your doctor before taking any of them. This is also true for any over-the-counter (prescription-free) medicine that you take.

How well do blood-sugar-lowering tablets (antidiabetics) work?

If you can’t lower your blood sugar enough by changing your lifestyle, you can take tablets known as antidiabetics. If one type of medication isn’t enough on its own, it can be combined with other blood-sugar-lowering tablets.

Research has shown that keeping blood sugar levels down reduces the risk of damage to small blood vessels, particularly in the eye. But it’s not clear how well antidiabetics help to prevent complications such as heart attacks and strokes. There are hardly any long-term studies in this area. There also isn’t enough research on how the different medications compare.

All antidiabetics can cause blood sugar levels to drop too low sometimes. Too-low blood sugar is known as hypoglycemia.

Types of antidiabetic drugs

Medications for type 2 diabetes (antidiabetics) include:

• Metformin: This drug reduces the amount of glucose produced by the body, and has been used for a long time. It is the best studied diabetes medication, as well as one of the best tolerated. For this reason, doctors usually recommend trying metformin first. The possible side effects include diarrhea and feeling unwell, especially if metformin isn’t taken together with a meal. In very rare cases (about 1 out of 10,000 per year), people with type 2 diabetes who take metformin develop acidosis. This is the medical term for too much acid in the blood, which can lead to breathing problems, nausea or circulatory shock. People with decreased kidney function, heart failure or an alcohol dependence have an increased risk of acidosis. For this reason, they aren’t usually allowed to take metformin.
• Sulfonylureas: These drugs help the body to produce more insulin. Like metformin, they have also been in use for quite a while. Episodes of hypoglycemia are a bit more common when using sulfonylureas than when using metformin. Some people also gain weight when they start the treatment. Others may have allergic reactions to sulfonylureas.
• Glitazones: Treatment with glitazones aims to strengthen the effect of the insulin made in your body. Pioglitazone is the only glitazone that is still on the market. Compared to sulfonylureas, pioglitazone is less likely to cause hypoglycemia. Possible side effects include weight gain, bone fractures, water retention and heart failure. Pioglitazone may slightly increase the risk of bladder cancer. Due to pioglitazone's potential side effects, it is not the drug of first choice.
• Glinides: Glinides include the drugs nateglinide and repaglinide. They increase insulin production in the body. Compared to metformin, glinides are more likely to lead to mild and moderate hypoglycemia. Glinides can cause weight gain.
• Gliptins (dipeptidyl peptidase-4 inhibitors): Gliptins also stimulate the production of insulin. They include the drugs linagliptin, saxagliptin, vildagliptin and sitagliptin. The possible side effects include headaches and gastrointestinal (stomach and bowel) problems.
• Gliflozins (SGLT2 inhibitors): Gliflozins include the drugs dapagliflozin, empagliflozin, ertugliflozin and canagliflozin. They cause more sugar to leave the body in urine, lowering blood sugar levels. Gliflozins can cause vaginal thrush and probably increase the risk of acidosis (too much acid in the blood).

Drugs known as alpha-glucosidase inhibitors were used in the treatment of type 2 diabetes in the past, but they are rarely used for this purpose nowadays. They slow down the uptake of sugar in the bowel. The most commonly used drug in this group is called acarbose. It causes a lot of side effects, particularly flatulence ("wind") and diarrhea. Compared to the other options, it doesn’t lower blood sugar levels as much.

When is insulin needed?

All people with type 1 diabetes have to inject insulin. People with type 2 diabetes usually only need insulin if treatment with tablets doesn't reduce their blood sugar levels enough. That is rarely the case, though.

Two different types of insulin are available: human insulin and insulin analogues. Both are genetically engineered, but have different chemical structures. Short-acting insulin analogues can lower blood sugar a bit faster than human insulin can. But there's no proof that this has any added health benefits. Human insulin and insulin analogues work equally well in the treatment of type 2 diabetes.

Several studies have looked into whether it makes more sense to use insulin or a combination of different antidiabetic drugs if blood sugar can’t be lowered enough by using a single antidiabetic drug and/or making changes to your diet and exercise habits. This is what was found:

• There was no difference between insulin and combinations of antidiabetics in terms of the long-term consequences of diabetes, such as heart problems.
• Insulin was better at lowering blood sugar.
• In people who took antidiabetic drugs, hypoglycemia was less common, but other side effects were more common – particularly stomach and bowel problems.

What are incretin mimetics?

Incretin mimetics are hormone-like drugs that can be injected in addition to taking metformin and/or sulfonylurea tablets. They stimulate the pancreas to make more insulin. Examples of these drugs include liraglutide, dulaglutide, lixisenatide, exenatide, semaglutide and albiglutide.

Incretin mimetics are not supposed to be used instead of antidiabetic tablets, but can be used instead of, or in addition to, insulin. These drugs are injected under the skin with a pre-filled pen. It is not yet clear whether treatment with incretin mimetics has any long-term advantages. The possible side effects include nausea and vomiting.

Which medication is most suitable?

Blood-sugar-lowering drugs aren't always a suitable treatment for everyone who has diabetes. Whether or not a person needs to take antidiabetic medication at all – and which drugs are most suitable – depends on a number of different factors:

• The person's treatment goal
• Their age
• Their general health
• Whether they have other medical conditions
• Whether they are taking other medications
• How well a drug works and how well it is tolerated

How much should blood sugar levels be reduced?

To see how well your blood sugar levels are regulated over the longer term, doctors can measure your HbA1c values. This value is a measure of the average blood sugar levels over the last two to three months. The HbA1c value is usually below 6% in people who don’t have diabetes and above 6% in people who do.

The target value will depend on various factors, including your age and any other illnesses you may have. Many people are advised to reduce their blood sugar to an HbA1c value between 6.5 and 7.5%. But lowering it to 8.5% or less may be enough too, particularly in older people who have other medical conditions. This is because very low values could have more disadvantages than advantages for them: For instance, they may have to take more medication to achieve lower HbA1c values. Then they will probably have more episodes of hypoglycemia (low blood sugar) too.

So the target HbA1c value has to be determined individually for each person.

Sources

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• Bolen S, Tseng E, Hutfless S et al. Diabetes Medications for Adults With Type 2 Diabetes: An Update. 2016.
• Bundesärztekammer (BÄK), Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Nationale Versorgungsleitlinie: Therapie des Typ-2-Diabetes. S3-Leitlinie. AWMF-Registernr.: nvl-001g. 2023.
• European Medicines Agency (EMA). European Medicines Agency clarifies opinion on pioglitazone and the risk of bladder cancer. 2011.
• Fullerton B, Siebenhofer A, Jeitler K et al. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. Cochrane Database Syst Rev 2018; (12): CD013228. [PMC free article: PMC6517032] [PubMed: 30556900]
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• Peterson SC, Barry AR. Effect of glucagon-like peptide-1 receptor agonists on all-cause mortality and cardiovascular outcomes: A meta-analysis. Curr Diabetes Rev 2018; 14(3): 273-279. [PubMed: 28413990]

• IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

  Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. informedhealth.org can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

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