That reading is understandable, and it is not what the evidence says. Type 2 diabetes tends to progress as beta-cell function declines (Chapter 3), so treatment plans are expected to change over the years. Current guidelines treat medicines as tools, chosen for specific goals: lowering glucose, protecting the heart and kidneys, managing weight, avoiding low glucose, and keeping treatment affordable. In type 1 diabetes, insulin is not one option among several. It is what keeps the body running.

This chapter describes what the main medicines do. It does not tell you what to take, how much, or when: those decisions belong to you and your care team, who know your kidneys, your other medicines, your budget and your daily life. No doses appear in this book, and none should be inferred from it. Section 11.1 explains the main medicine classes and how guidelines think about choosing between them. Section 11.2 covers insulin in plain language, including types, delivery, cost and access. Section 11.3 covers living with these medicines safely: missed doses, illness, alcohol, driving, travel, fasting, and the questions worth taking to your next appointment.

11.1 The Medicine Landscape in Type 2 Diabetes

Medicines sit beside food, movement and sleep

The American Diabetes Association (ADA) advises starting medication at diagnosis, without delay unless there is a reason not to, alongside healthy behaviours and diabetes education.[@ada2026s9] That does not mean lifestyle has failed. Type 2 diabetes involves several problems at once (Chapter 1), and the ADA and the European Association for the Study of Diabetes (EASD) describe combination therapy as a way to keep glucose in range for longer.[@davies2022] Targets are individual: the ADA calls an HbA1c below 7% (53 mmol/mol) appropriate for many non-pregnant adults, and looser goals suitable where tight control is risky.[@ada2026s6]

The main classes at a glance

Each class works in a different place (Figure 11.1).

{{fig:F11-A}}

Summarised by the author from the ADA Standards of Care 2026 (Table 9.2 and text)[@ada2026s9] and the IDF-DAR 2021 descriptions of how each class works.[@idfdar2021] "Unlikely" means the medicine alone rarely causes low glucose; the risk rises when combined with a sulfonylurea or insulin. Doses and brand names are left out on purpose.

On HbA1c, the ADA summarises comparative analyses this way: each new oral class added to metformin generally lowers it by about 0.7 to 1.0 percentage points (8 to 11 mmol/mol), and adding a GLP-1 agonist or dual GIP/GLP-1 agonist usually lowers it by 1 to 2 points or more.[@ada2026s9] These are trial averages, not promises for one person.

What the guidelines say, and what they do not

Metformin has long been the usual first medicine: the ADA describes it as effective, safe for most people, inexpensive and widely available, and associated with lower risks of microvascular complications, cardiovascular events and death.[@ada2026s9] Beyond that, guidelines describe situations, and your team weighs several at once:

• Heart and blood-vessel disease, established or high-risk. A GLP-1 agonist and/or SGLT2 inhibitor with proven heart benefit, whatever the HbA1c.[@ada2026s9]
• Heart failure. An SGLT2 inhibitor, for glucose management and to prevent hospital admissions.[@ada2026s9]
• Chronic kidney disease (CKD). An SGLT2 inhibitor or a GLP-1 agonist with proven benefit.[@ada2026s9] The 2022 KDIGO kidney guideline strongly recommends an SGLT2 inhibitor for type 2 diabetes with CKD and adequate kidney function, and a long-acting GLP-1 agonist if targets are not met or those medicines cannot be used.[@kdigo2022]
• Excess weight. Semaglutide and tirzepatide have the highest efficacy for glucose and weight; sulfonylureas, pioglitazone and insulin tend to add weight.[@ada2026s9]
• Cost. The ADA lists metformin, sulfonylureas, pioglitazone and human insulin as lower-cost options within the context of their risks.[@ada2026s9] The ADA/EASD report accepts that SGLT2 inhibitors and GLP-1 agonists are expensive, and that where resources are limited they may need to go first to people at highest risk.[@davies2022]

None of this ranks medicines for you. In the five-year GRADE trial of four add-on medicines, all lowered HbA1c; a long-acting insulin and a GLP-1 agonist were modestly better at keeping it below 7%, a DPP-4 inhibitor was the least effective, and severe lows were more common with the insulin and the sulfonylurea.[@ada2026s9] Differences were modest, and a plan built on older, cheaper medicines can be a sound plan.

Science Corner: Organ protection is not the same as glucose lowering The ADA/EASD report asks clinicians not to confuse choosing a medicine for its glucose-lowering effect with choosing it to protect the heart and kidneys. SGLT2 inhibitors protect those organs partly independently of glucose, including in people without diabetes.[@davies2022] KDIGO makes the same point: its SGLT2 recommendation is for kidney and heart protection and applies to people with CKD even without type 2 diabetes.[@kdigo2022] That is why someone whose HbA1c is already on target may still be offered one.

"Insulin means I failed" is a myth

Chapter 3 introduced this myth; the ADA now addresses it directly. The progressive nature of type 2 diabetes should be explained openly, and clinicians should avoid using insulin as a threat or describing it as a sign of personal failure. Insulin is also used temporarily, for instance in hospital, acute illness or high-dose steroid treatment, and once the harm of very high glucose eases, plans can often be simplified.[@ada2026s9] Fear of insulin is common: in one study, more than a quarter of people with type 2 diabetes not yet on insulin said they would be unwilling to start it.[@polonsky2005] You are allowed to be nervous, and to say so.

Medicines that push glucose the other way

Some medicines raise glucose, including steroids and some cancer and transplant drugs (Chapter 10). Steroid-related highs vary with drug, timing and dose, and can be missed if glucose is checked only in the morning.[@ada2026s9] Tell every prescriber you have diabetes, and your diabetes team about any new medicine.

11.2 Insulin in Plain Language

What insulin does, and why it is injected

In Chapter 1, insulin was the doorbell that tells cells to open their glucose doors. Insulin is a protein that digestion would break down if it were swallowed, which is why it is traditionally injected under the skin. An inhaled form exists, but it is not suitable for people with chronic lung disease or who smoke, and lung function must be tested before and after starting it.[@ada2026s9]

Insulin types by how they act

Insulins are grouped by how fast they start and how long they last. Table 11.1 gives relative descriptions only; real timing differs by product, injection site and person, and your team or pharmacist can tell you what applies to yours.

Qualitative summary by the author from the ADA Standards of Care 2026 (Section 9 text and Table 9.1).[@ada2026s9] Concentrated insulins also exist and come in pens to reduce dosing errors, so check the strength on the label and ask your pharmacist if you are switched.[@ada2026s9]

{{fig:F11-B}}

Basal, mealtime and correction insulin

Basal insulin is the background supply; in type 2 diabetes its main action is to restrain the liver's glucose production overnight and between meals.[@ada2026s9] Mealtime insulin covers the glucose that arrives with food. Correction insulin adjusts a reading above target.

Type 1 diabetes. Most adults use multiple daily injections (a long-acting insulin plus mealtime insulin) or a pump. Insulin can never simply be stopped, because without it ketoacidosis develops (Chapter 13).[@ada2026s9] The ADA advises analogues over human insulins for most adults with type 1 diabetes to reduce lows,[@ada2026s9] while the World Health Organization (WHO) notes that human insulin is in general as effective and much cheaper, which matters for access (below).[@who2021insulin]

Type 2 diabetes. Insulin is added when other medicines are not enough, or earlier when glucose is very high. The ADA gives examples such as an HbA1c above 10%, glucose of 300 mg/dL (16.7 mmol/L) or more, or symptoms of high glucose.[@ada2026s9] When glucose is not severely high, the ADA prefers a GLP-1-based medicine to insulin, mainly for lower low-glucose risk and weight effects, though cost and tolerability matter; if insulin is used, adding a GLP-1 agonist improves effectiveness.[@ada2026s9] Basal insulin is usually the first step; mealtime insulin follows only if needed.

Why the care team sets the doses. Insulin needs change with food, activity, illness, sleep, kidney function and other medicines, so doses are personal and reviewed regularly. The ADA describes "overbasalisation" (too much background insulin, masking a need for mealtime cover) as a pattern that shows up as large gaps between bedtime and morning readings or as lows, and asks teams to reassess.[@ada2026s9] It is a reason to bring your readings to the team, not to self-adjust.

Science Corner: The trade-off that shaped modern insulin therapy In the Diabetes Control and Complications Trial (DCCT), intensive insulin treatment in type 1 diabetes brought average HbA1c to 7.3% versus 9.1% with conventional treatment, and cut microvascular complications by about half over six years. It cost something: severe low glucose occurred at 62 episodes per 100 person-years versus 19.[@ada2026s9][@dcct1993] Benefits persisted for at least 20 years afterwards.[@ada2026s9] That trade-off is why modern insulins, sensors and pumps aim to make tight control safer.

Getting insulin in: technique matters

The ADA prefers pens in most cases for people who inject several times a day, and recommends pens or injection aids for people with dexterity or vision problems.[@ada2026s7] Technique affects results more than most people expect:

• Fat, not muscle. Insulin belongs in the fat layer under the skin. Injection into muscle can make absorption unpredictable and is associated with frequent, unexplained lows. Short 4-mm needles reduce this risk across ages and body types, including in adults with obesity.[@ada2026s9]
• Rotate sites. Recommended sites are the abdomen, thigh, buttock and upper arm. Repeated injections in one spot can cause lipohypertrophy, soft raised areas several centimetres across that make absorption erratic and cause unexplained highs, swings and lows.[@ada2026s9] Ask your nurse to look at and feel your sites at reviews.

{{fig:F11-C}}

Storage. Keep unopened insulin in a refrigerator, never frozen, and away from direct heat and sunlight.[@fda2017insulin][@nhsinsulin] The FDA notes that, for the US products it covers, insulin in vials or cartridges can stay unrefrigerated for up to 28 days and continue to work, but that heat over time reduces its effect.[@fda2017insulin] Times differ by product, so check your label, and ask your pharmacist if your climate is hot or your fridge unreliable.

Pumps and automated insulin delivery

An insulin pump delivers rapid-acting insulin continuously, with extra amounts at meals. An automated insulin delivery (AID) system links a pump, a continuous glucose sensor and a program that adjusts delivery in real time.[@ada2026s9] For type 1 diabetes the ADA prefers AID for people who can use it safely, because such systems consistently improve time in range and reduce lows, and says it should be offered to all adults on insulin, type 1 or type 2, depending on needs and preferences.[@ada2026s9][@ada2026s7] The trade-offs are real: pumps are the most expensive plan, are worn continuously, are technically demanding, and carry a risk of fast-developing ketosis if delivery is interrupted.[@ada2026s9] Training is essential.[@ada2026s7] Chapter 12 covers sensors and devices.

Cost and access: a global issue

Insulin was discovered over a century ago, yet access remains uneven. WHO estimates that nine million people with type 1 diabetes depend on insulin, and more than 60 million with type 2 diabetes need it, but one in two of the latter does not get it.[@who2021insulin] WHO's 2021 report named high prices, low availability of human insulin, three companies holding more than 90% of the market, and weak health systems. Analogues cost at least 1.5 times as much as human insulin, and biosimilars (essentially generic versions) could be more than 25% cheaper than originator products.[@who2021insulin] In 2026 WHO extended its quality-assurance pathway to analogues to add competition in lower-income countries.[@who2026prequal]

You can ask questions without shame:

• Is human insulin an option for me, and what would we gain or lose compared with an analogue?
• Is there a biosimilar or lower-cost product my pharmacy stocks?
• If I cannot afford my next refill, what should I do before I run short?

The last matters most. The ADA lists insulin rationing as a risk factor for diabetic ketoacidosis,[@ada2026s6] and advises teams to screen everyone for cost barriers and to work with pharmacists and social workers to reduce them.[@ada2026s9] The ADA also says glucagon, the emergency medicine for severe lows, should be prescribed to everyone taking insulin, with family and colleagues taught where it is and how to use it; Chapter 13 explains.[@ada2026s9]

11.3 Living With Medicines Safely

Which medicines can cause low glucose

The ADA classes people treated with insulin, sulfonylureas or meglitinides (a related class) as at risk of hypoglycaemia; clinically significant lows are rare with other classes. Rates are highest with intensive insulin, then basal insulin, then sulfonylureas and meglitinides, and combining insulin with a sulfonylurea adds risk. Kidney disease, age 75 or over, alcohol or substance use disorder, food insecurity, and fasting for religious or cultural reasons also raise it.[@ada2026s6] Some antibiotics and antifungals can markedly increase the effect of a sulfonylurea, so tell every prescriber and pharmacist what you take.[@ada2026s6]

Chapter 13 explains how to recognise and treat lows. Food and activity changes can shift how these medicines behave: cutting carbohydrate, eating cooled rice, changing meal order or timing, or starting exercise (Chapters 5, 6, 8 and 9). The ADA/EASD report says people on insulin or a sulfonylurea should be educated about hypoglycaemia when they change their activity or nutrition plan.[@davies2022] Tell your team before a big change. When a GLP-1-based medicine is added, teams usually reassess the sulfonylurea and insulin to limit lows.[@ada2026s9]

Missed doses without blame

WHO found that adherence to long-term treatment averages about 50% in developed countries and is lower in developing ones, that the word "compliance" is too closely tied to blame, and that adherence depends on five groups of factors: social and economic, the health system, the condition, the treatment, and the person.[@who2003adh] The ADA/EASD report says medication-taking problems affect almost half of people with type 2 diabetes, commonly because of doubts that the medicine works, fear of low glucose, difficulty getting supplies, and side effects; complexity and cost add to it.[@davies2022] In a survey at one US diabetes centre, 51 of 199 respondents (25.5%) had used less insulin than prescribed, stretched it or skipped it because of cost in the past year, which was associated with poorer control.[@herkert2019]

A missed dose is information, not a moral failing. Tell your team what you actually take and what gets in the way; they can often simplify a plan, change the product or timing, lower costs or treat side effects. Ask what to do if you miss a dose before it happens, since advice varies by medicine.

Some people, especially with type 1 diabetes, limit insulin from fear of weight gain. The ADA reports a median prevalence of insulin restriction for weight control of 15% and lists it among disordered eating behaviours to screen for, without stigma.[@ada2026s5] It is dangerous because it raises the risk of ketoacidosis, and it responds to treatment. Please tell your team; Chapter 16 returns to it.

Sick days, surgery, and one rare but serious warning

When you are ill and cannot eat or drink normally, some medicines may need to pause. The ADA says clinicians should consider holding metformin and SGLT2 inhibitors if intake cannot be maintained or kidney injury is a concern, and GLP-1 agonists in illness with marked stomach symptoms. But people on insulin should not stop background insulin just because they are not eating, and should call their team for instructions.[@ada2026s6] Ask now for a written sick-day plan naming each medicine (Chapter 13). Before surgery, tell the team every medicine you use: SGLT2 inhibitors are usually paused beforehand, and GLP-1 agonists need guidance because of an anaesthetic risk.[@ada2026s9][@kdigo2022]

The SGLT2 warning. Diabetic ketoacidosis (DKA), a dangerous build-up of acids called ketones, is uncommon in type 2 diabetes on SGLT2 inhibitors (an estimated 0.6 to 4.9 events per 1,000 person-years) but can happen. Risk factors include very-low-carbohydrate or ketogenic eating, prolonged fasting, dehydration and excessive alcohol. It can occur with near-normal glucose: up to a third of people who developed DKA on these medicines had glucose below 200 mg/dL (11.1 mmol/L). The ADA advises teaching the signs, providing ketone-testing tools, and avoiding ketogenic diets; the ADA says people who have had DKA should not be treated with them.[@ada2026s9] Signs of a hyperglycaemic crisis include frequent urination, marked thirst, weight loss, vomiting, dehydration and a change in alertness or thinking.[@ada2026s6] If you have these, seek urgent medical care and say which medicines you take.

Alcohol, driving and travel

Alcohol can cause low glucose, including delayed lows hours later, particularly with insulin or sulfonylureas; the ADA advises checking glucose before and after drinking, cites WHO's position that no level of alcohol is safe, and advises avoiding excessive drinking on SGLT2 inhibitors.[@ada2026s5]

Driving. A diagnosis of diabetes does not by itself say anything about whether you can drive safely, and most people with diabetes drive safely.[@ada2014driving][@cox2024driving] For people at risk of lows, the ADA advises carrying a meter and quick sugar in the vehicle, stopping as soon as symptoms appear, and not driving again until glucose and thinking have recovered, which can take 30 to 60 minutes.[@ada2014driving] Rules differ by country, so ask your team, especially after starting insulin.

Travel. Carry insulin, medicines and testing supplies in hand luggage, bring extra in case of delays, and take a letter from your care team.[@nhsinsulin][@dukravel] Before crossing several time zones, ask your team how to plan insulin and other medicines and how to set the time on a pump or sensor, and find out where you could get insulin at your destination.[@nhsinsulin][@dukravel]

Fasting and Ramadan

The IDF-DAR guideline recommends a medical assessment ideally 6 to 8 weeks before Ramadan and a three-level risk score (low, moderate, high) that counts diabetes type, complications, low-glucose history and treatment, with insulin and sulfonylureas adding to the score. High-risk people are advised not to fast; moderate-risk people are advised against it, though many will decide to fast and should do so with medical advice; low-risk people should generally be able to fast; pregnant and breastfeeding women have the right not to fast.[@idfdar2021] The guideline says people taking sulfonylureas, other insulin-releasing tablets or insulin will need treatment adjustments to reduce low glucose, and advises caution with SGLT2 inhibitors because of dehydration. It tells everyone who fasts to break the fast if glucose falls below 70 mg/dL (3.9 mmol/L) or rises above 300 mg/dL (16.6 mmol/L), or if symptoms of a low or of acute illness appear.[@idfdar2021] Adjustments are for your team, and the same applies to other fasts.

Pregnancy, weight-loss medicines, and stepping down

Pregnancy. Evidence for noninsulin diabetes medicines in pregnancy is limited. The ADA advises contraception counselling, since some medicines (tirzepatide, for example) can lower oral contraceptive levels around starting and dose increases, and planning before pregnancy, including when to stop noninsulin medicines.[@ada2026s9] Weight-loss medicines are contraindicated in pregnancy.[@ada2026s8]

Weight-loss medicines. For people with type 2 diabetes and overweight or obesity, the ADA recommends considering weight-loss medicines alongside lifestyle change, preferring semaglutide or tirzepatide. In the STEP 2 trial semaglutide gave 6.2% more weight loss than placebo and an HbA1c 1.2 points lower at 68 weeks; in SURMOUNT-2, tirzepatide gave 9.6% and 11.6% more weight loss than placebo at two dose levels, with HbA1c 1.55 and 1.57 points lower at 72 weeks.[@ada2026s8] The dual agonist also reduced sleep apnoea severity in two trials of adults with obesity, as Chapter 10 noted.[@ada2026s5] These medicines are meant to be continued: after sudden discontinuation in trials, people regained one-half to two-thirds of the lost weight within a year and metabolic gains reversed.[@ada2026s8] Discuss stopping, dose and nutrition with your prescriber. The ADA advises against non-approved compounded versions because their content is uncertain, and reports counterfeits; if a medicine is in short supply, ask about switching to another approved one.[@ada2026s9]

Stepping down. Plans can be reduced as well as increased. The ADA says this may be appropriate when weight loss and lifestyle change mean fewer medicines are needed, or when a medicine causes side effects or lows, starting with those lacking heart or kidney benefit;[@ada2026s9] trials show it can be done safely.[@ada2026s6] Remission, defined by international consensus as an HbA1c below 6.5% at least three months after stopping all glucose-lowering medicines, is possible for some, for instance after sustained weight loss above 10% or a supervised programme like DiRECT (Chapter 3), and needs yearly follow-up.[@riddle2021][@ada2026s8][@lean2018] Never stop medicine on your own hoping to reach remission.

Questions to ask your care team

• What is each of my medicines for, and how will we know it is working?
• Which can cause low glucose, and what should I do if it happens?
• Which side effects are urgent?
• What is my sick-day plan, and which medicines must never be stopped?
• How should alcohol, driving, travel and fasting change my plan?
• Are cheaper or simpler options available, and what would we give up?
• Could any of my other medicines (steroids, antibiotics, antipsychotics) affect my glucose?
• If I miss a dose, what should I do next time, and can I tell you without being judged?

Key Takeaways

• Diabetes medicines are tools for specific goals: glucose, heart and kidney protection, weight, safety and cost. Type 2 diabetes tends to progress, so plans change, and that is not failure.
• The classes act in different places, with different effects on weight, lows, heart and kidney. Guidelines describe situations where a class is favoured, not a ranking for individuals.
• Insulin, sulfonylureas and meglitinides are the classes most linked with low glucose. Changes in food, activity, alcohol or fasting can shift the risk, so plan them with your team.
• Insulin types differ mainly in speed and length of action. Technique matters: fat not muscle, rotating sites, checking for lumps, and proper storage.
• Insulin access is a global problem: WHO estimates one in two people with type 2 diabetes who need insulin do not get it. Ask about human insulin, biosimilars and assistance, and never ration insulin quietly.
• Missed doses are common and usually have understandable causes, such as cost, fear, side effects and complexity. Telling your team is the first step to fixing them.
• SGLT2 inhibitors can rarely cause ketoacidosis even with near-normal glucose. Seek urgent care for vomiting, dehydration or a change in alertness.

Action Points

1. List every medicine you use. Write down each medicine, what it is for and who prescribed it, including steroids and over-the-counter products, and bring the list to every appointment.
2. Ask for a written sick-day plan. It should name each medicine, say which to hold and which never to stop, and say when to call or go for urgent care.
3. Tell your team about barriers. If cost, fear of injections, side effects or complexity make doses hard, say so and ask for cheaper, simpler or better-tolerated options.
4. If you use insulin, check sites and storage. Ask a nurse to examine your injection sites, and check the storage advice on your own label, especially in hot weather or when travelling.
5. Plan changes before you make them. Before fasting, travel, a new diet, heavy exercise or a new medicine, ask how your medicines should be handled, and do not change any medicine on your own.

This book is intended for education and does not replace personal medical advice. If you have diabetes or take glucose-lowering medication, please consult your healthcare team before changing your diet, exercise, or treatment.