Insulin treatment regimens in type 1 diabetes

The basal-bolus regimen tries to mimic the normal functioning of the pancreas using two types of insulin [1]. Basal (long-acting) insulin keeps blood glucose stable between meals and overnight, while you give rapid-acting insulin boluses for each meal and for corrections. Basal insulin generally accounts for 30–50% of the daily requirement [2]. This regimen offers you the greatest flexibility in choosing when and what to eat.

With the basal-bolus regimen you take a minimum of four injections per day, but you achieve the best glycemic control possible with injections [3]. You can make fine adjustments whenever you want. For example, you can skip a meal, eat more or less, make corrections when you need to. It is the gold standard regimen for administering insulin injections in type 1 diabetes because it comes closest to normal pancreatic function, as the figure below shows [1].

With the basal-bolus regimen you take at least four injections a day [2]. You take one long-acting insulin injection and one rapid-acting insulin injection for each of the three main meals [4]. In reality, most patients take more than six injections by adding corrections for hyperglycemia or boluses for snacks.

There is no such thing as "too many" injections if they improve your control. Some highly motivated people take ten injections daily for the best possible glycemic control. Insulin pumps replace multiple injections with hundreds of micro-doses per day, although the infusion set still has to be changed every few days, which also involves a needle prick [5]. The important thing is to take enough injections to keep your blood glucose on target, not to minimize their number.

The intensive physiological regimen means actively and frequently adjusting your insulin doses according to blood glucose, carbohydrates, physical activity, and other factors [6]. It includes a minimum of four injections per day (or a pump), measuring blood glucose at least four times per day, and precise dose calculation. You don't follow fixed doses, but adapt each dose to the current situation. For this you use insulin-to-carbohydrate ratios (how many grams of carbohydrate one unit of insulin covers) and correction factors (how much one unit of insulin lowers blood glucose). Both differ across time intervals [3].

The intensive physiological regimen requires solid diabetes education, but offers the best control and the greatest freedom. Compared with conventional treatment, it significantly reduces long-term complications [6]. It requires dedication and continuous learning. It is the only regimen currently recommended for type 1 diabetes [4].

It is not a suitable regimen today. The two-injection regimen (mixed insulin in the morning and evening) is outdated and inadequate for most people with type 1 diabetes [6]. It provides poor glycemic control, requires meals and snacks at fixed times, and does not allow flexibility [4]. It may be temporarily acceptable only in special situations, such as elderly people with severe cognitive problems.

With only two injections you cannot correct hyperglycemia or adapt doses to meal content. You also risk frequent hypoglycemia due to the action peaks of NPH (neutral protamine Hagedorn) insulin (an intermediate-acting human insulin) [1]. HbA1c will probably be above 8% (64 mmol/mol) and the risk of complications consequently increases significantly [6]. If your doctor proposes this regimen for type 1 diabetes, ask what the reason for this choice is and how long the regimen is meant to last. If anything remains unclear, you can also seek a second opinion from another diabetologist.

If you forget your mealtime rapid-acting insulin and remember within the first hour, the full dose can be taken immediately, according to the protocol agreed with the medical team. Between one and three hours, check your blood glucose and be cautious with additional doses to avoid insulin overlap ("stacking") [4]. After three hours from the meal, do not take the meal dose any longer, only a correction based on your current blood glucose. Check your blood glucose two hours after taking the correction and monitor carefully for the next 12 hours. Hypoglycemia means a blood glucose below 70 mg/dL (3.9 mmol/L): you take 15 g of fast-acting carbohydrate and recheck after 15 minutes. The complete steps are on the pages about what hypoglycemia is and about how to treat it.

If you missed your dose of insulin glargine (or of another basal insulin lasting about 24 hours), you can take it as soon as you remember [4]. In the following days, gradually shift the administration time back to your usual time. Alternatively, you can take several doses of rapid-acting insulin until the usual time of your basal insulin. You and your doctor decide which option suits you best. In this situation, to be on the safe side, check for ketones whenever your glucose is above 200 mg/dL (11.1 mmol/L) [7]. For insulin degludec (a basal insulin with a very long duration of action), if you have forgotten your evening dose, you can take it in the morning. Return to your usual evening time only once your doctor's minimum interval between two doses has passed. Two doses given too close together increase the risk of hypoglycemia [1]. Monitor your blood glucose carefully and make corrections with rapid-acting insulin if needed.

The regimen and the titration steps are decided together with your medical team. Dose adjustment is done gradually, changing the dose very little and waiting a few days to see the effect. For basal insulin, if blood glucose rises or falls too much overnight, the adjustment is usually 1–2 units, according to the plan agreed with the medical team [4]. For meal boluses, if blood glucose two hours after a meal is consistently too high or too low, modify the insulin-to-carbohydrate ratio.

Keep a detailed log with blood glucose readings, doses, carbohydrates, and activities to identify patterns [8]. The general rule is that if you see the same pattern for several days in a row, make a small adjustment. Don't make big changes. Small and repeated adjustments are better [9]. Learn to distinguish between an atypical day and a real trend that truly requires an adjustment.

Children use the same basal-bolus regimens as adults, but with age-specific features [3]. Doses are much smaller and require frequent adjustments. Sometimes insulin dilutions are used for very small doses [10]. The insulin pump is ideal for children because of the small doses needed, but also for the precision and flexibility it offers [5].

Parents must be taught to manage the tendency toward high glycemic variability [10]. Children's physical activity is sometimes unpredictable, their meals are irregular, and they quite often catch the usual childhood illnesses. Adolescents need higher doses because of the insulin resistance associated with puberty, sometimes reaching 1–2 units/kg/day [3]. The regimen must allow the child progressive autonomy, gradually learning to manage their diabetes on their own.

The insulin pump offers clear advantages: more precise dosing, programmable basal rates for different times of day, extended boluses for complex meals, and the elimination of multiple injections [5]. With the standard pump, HbA1c is similar or slightly better, but severe hypoglycemic episodes are fewer and glycemic variability is lower [11]. Quality of life is usually better with the pump. Nevertheless, the standard pump does not guarantee better control [12].

Some people achieve excellent control with insulin pens and prefer not to be "connected" permanently to a device. The pump is more expensive and requires technical training. The best option is the one you use correctly and consistently. The exception is the pump capable of closed-loop operation (with automatic insulin adjustment based on sensor readings). It usually offers better control than external injections, when it is available and suited to your situation [5].

Not instead of insulin. In type 1 diabetes the pancreas no longer makes insulin, and no medicine in this class replaces that. What has been studied is adding it to insulin, in patients with type 1 diabetes and excess weight. Pooled results show a weight loss of about 4 kg and a small drop in HbA1c, of roughly 0.25 percentage points. The insulin requirement falls by almost 10 units a day [13]. In newer studies, semaglutide lowered weight by 8.8 kg in people using an automated insulin system, and tirzepatide lowered it by 10.1% over 8 months [14].

The price shows up in the same data: hypoglycemia was more frequent, and nausea and vomiting appeared significantly more often [13]. For treating diabetes, the class is not approved in type 1 diabetes, and the evidence comes from small studies or from everyday practice. Liraglutide, semaglutide and tirzepatide, however, are also approved for obesity, and the obesity labeling does not exclude type 1 diabetes. So a doctor may recommend them for some people with type 1 diabetes and obesity, with close follow-up [14]. One large phase 3 trial is under way [15]. If it is started, insulin doses are reduced from the outset, with ketone bodies watched closely.