Medications used to treat diabetes do so by lowering blood sugar levels. There are a number of different classes of anti-diabetic medications. Some are available by mouth, such as metformin, while others are only available by injection such as GLP-1 agonists. Type 1 diabetes can only be treated with insulin, typically with a combination of regular and NPH insulin, or synthetic insulin analogs.

Metformin is generally recommended as a first line treatment for type 2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the liver's production of glucose. Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type II DM. These include agents that increase insulin release, agents that decrease absorption of sugar from the intestines, and agents that make the body more sensitive to insulin. When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are then increased to effect.

Since cardiovascular disease is a serious complication associated with diabetes, some have recommended blood pressure levels below 130/80 mmHg. However, evidence supports less than or equal to somewhere between 140/90 mmHg to 160/100 mmHg; the only additional benefit found for blood pressure targets beneath this range was an isolated decrease in stroke risk, and this was accompanied by an increased risk of other serious adverse events. A 2016 review found potential harm to treating lower than 140 mmHg. Among medications that lower blood pressure, angiotensin converting enzyme inhibitors (ACEIs) improve outcomes in those with DM while the similar medications angiotensin receptor blockers (ARBs) do not. Aspirin is also recommended for people with cardiovascular problems, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.

Injections of insulin—either via subcutaneous injection or insulin pump— are necessary for those living with type 1 diabetes because it cannot be treated by diet and exercise alone. Insulin dosage is adjusted taking into account food intake, blood glucose levels and physical activity.

Untreated type 1 diabetes can commonly lead to diabetic ketoacidosis which is a diabetic coma which can be fatal if untreated. Diabetic ketoacidosis can cause cerebral edema (accumulation of liquid in the brain). This is a life-threatening issue and children are at a higher risk for cerebral edema than adults, causing ketoacidosis to be the most common cause of death in pediatric diabetes.

Treatment of diabetes focuses on lowering blood sugar or glucose (BG) to the near normal range, approximately 80–140 mg/dl (4.4–7.8 mmol/L). The ultimate goal of normalizing BG is to avoid long-term complications that affect the nervous system (e.g. peripheral neuropathy leading to pain and/or loss of feeling in the extremities), and the cardiovascular system (e.g. heart attacks, vision loss). This level of control over a prolonged period of time can be varied by a target HbA level of less than 7.5%.

There are four main types of insulin: rapid acting insulin, short-acting insulin, intermediate-acting insulin, and long-acting insulin. The rapid acting insulin is used as a bolus dosage. The action onsets in 15 minutes with peak actions in 30 to 90 minutes. Short acting insulin action onsets within 30 minutes with the peak action around 2 to 4 hours. Intermediate acting insulin action onsets within one to two hours with peak action of four to 10 hours. Long-acting insulin is usually given once per day. The action onset is roughly 1 to 2 hours with a sustained action of up to 24 hours. Some insulins are biosynthetic products produced using genetic recombination techniques; formerly, cattle or pig insulins were used, and even sometimes insulin from fish.

People with type 1 diabetes always need to use insulin, but treatment can lead to low BG (hypoglycemia), i.e. BG less than 70 mg/dl (3.9 mmol/l). Hypoglycemia is a very common occurrence in people with diabetes, usually the result of a mismatch in the balance among insulin, food and physical activity. Symptoms include excess sweating, excessive hunger, fainting, fatigue, lightheadedness and shakiness. Mild cases are self-treated by eating or drinking something high in sugar. Severe cases can lead to unconsciousness and are treated with intravenous glucose or injections with glucagon. Continuous glucose monitors can alert patients to the presence of dangerously high or low blood sugar levels, but technical issues have limited the effect these devices have had on clinical practice.

As of 2016 an artificial pancreas looks promising with safety issues still being studied.

In some cases, a pancreas transplant can restore proper glucose regulation. However, the surgery and accompanying immunosuppression required may be more dangerous than continued insulin replacement therapy, so is generally only used with or some time after a kidney transplant. One reason for this is that introducing a new kidney requires taking immunosuppressive drugs such as cyclosporine, which allows the introduction of a new pancreas to a person with diabetes without any additional immunosuppressive therapy. However, pancreas transplants alone may be beneficial in people with extremely labile type 1 diabetes mellitus.

Oral medications like Glipizide that stimulate the pancreas, promoting insulin release (or in some cases, reduce glucose production), are less and less used in cats, and these drugs may be completely ineffective if the pancreas is not working. These drugs have also been shown in some studies to damage the pancreas further or to cause liver damage. Some owners are reluctant to switch from pills to insulin injections, but the fear is unjustified; the difference in cost and convenience is minor (most cats are easier to inject than to pill), and injections are more effective at treating the disease.

People with diabetes can benefit from education about the disease and treatment, good nutrition to achieve a normal body weight, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.

There is no single dietary pattern that is best for all people with diabetes. For overweight people with type 2 diabetes, any diet that the person will adhere to and achieve weight loss on is effective.

An acute hypoglycemic episode (very low blood sugar) can happen to even careful pet owners, since cats' insulin requirements sometimes change without warning. The symptoms include depression/lethargy, confusion/dizziness, loss of excretory/bladder control, vomiting, and then loss of consciousness and/or seizures. Immediate treatment includes administering honey or corn syrup by rubbing on the gums of the cat (even if unconscious, but not if in seizures). Symptomatic hypoglycemia in cats is a medical emergency and the cat will require professional medical attention. The honey/corn syrup should continue to be administered on the way to the vet, as every minute without blood sugar causes brain damage.

A cat with hypoglycemia according to a blood glucose meter (<2.2 mmol/L or 40 mg/dL), but with no symptoms, should be fed as soon as possible. Hypoglycemic cats that refuse to eat can be force-fed honey or corn syrup until they stabilize.

Mild hypoglycemic episodes can go unnoticed, or leave evidence such as urine pools outside the litter box. In these cases the blood sugar will probably appear paradoxically "high" upon the next test hours later, since the cat's body will react to the low blood sugar by stimulating the liver to release stored glycogen.

The administration of sodium bicarbonate solution to rapidly improve the acid levels in the blood is controversial. There is little evidence that it improves outcomes beyond standard therapy, and indeed some evidence that while it may improve the acidity of the blood, it may actually worsen acidity inside the body's cells and increase the risk of certain complications. Its use is therefore discouraged, although some guidelines recommend it for extreme acidosis (pH<6.9), and smaller amounts for severe acidosis (pH 6.9–7.0).

Cerebral edema, if associated with coma, often necessitates admission to intensive care, artificial ventilation, and close observation. The administration of fluids is slowed. The ideal treatment of cerebral edema in DKA is not established, but intravenous mannitol and hypertonic saline (3%) are used—as in some other forms of cerebral edema—in an attempt to reduce the swelling.

Food should be offered at the first signs of possible hypoglycemia. If the animal refuses it, a sugar solution (corn syrup, honey, pancake syrup, etc.) should be poured on the finger and rubbed on its gums or under the tongue (sublingually). The solution must be applied this way to prevent possible aspiration of it. Intervet suggests one tablespoon of a sugar solution rubbed onto the gums, regardless of the size of the dog. Another hypoglycemia formula is 1 gram of glucose for every kilogram (2.2 lb) of the animal's body weight. Since sugar acts quickly, a response should be seen within a minute or two.

Honey, syrup, or sugar, as simple carbohydrates, act rapidly and will make the blood glucose rise, but the rise will not last very long, as they are broken down quickly by the body. Feeding something containing complex carbohydrates when the pet is able to eat will make sure another hypoglycemia event does not overtake the rapid rise in blood glucose levels from the sugar solution. Complex carbohydrates take longer to be broken down by the body, so they do not raise blood glucose levels until some time after being eaten. A small meal should be fed and the animal taken for medical evaluation to determine if further treatment is needed. Treatment of a serious hypoglycemia episode is similar to that of diabetic humans: using glucose or glucagon infusions, depending on severity.

The goals of treatment are to slow the progression of kidney damage and control related complications. The main treatment, once proteinuria is established, is ACE inhibitor medications, which usually reduce proteinuria levels and slow the progression of diabetic nephropathy. Other issues that are important in the management of this condition include control of high blood pressure and blood sugar levels (see diabetes management), as well as the reduction of dietary salt intake.

Modulating and ameliorating diabetic complications may improve the overall quality of life for diabetic patients. For example; when elevated blood pressure was tightly controlled, diabetic related deaths were reduced by 32% compared to those with less controlled blood pressure.

In many cases, neonatal diabetes may be treated with oral sulfonylureas such as glyburide. Physicians may order genetic tests to determine whether or not transitioning from insulin to sulfonylurea drugs is appropriate for a patient.

The transfer from insulin injections to oral glibenclamide therapy seems highly effective for most patients and safe. This illuminates how the molecular understanding of some monogenic form of diabetes may lead to an unexpected change of the treatment in children. This is a spectacular example of how the pharmacogenomic approach improves in a tremendous way the quality of life of the young diabetic patients.

Insulin Therapy

- Long Acting Insulin: (Insulin glargine)-is a hormone that works by lowering levels of blood glucose. It starts to work several hours after an injection and keeps working for 24 hours. It is used to manage blood glucose of diabetics. It is used to treat Type 1 and 2 diabetes in adults and Type 1 diabetes in kids as young as 6 years old.

- Short Acting Insulin (e.g. Novolin or Velosulin)-It works similarly to natural insulin and takes up to 30 minutes and lasts for about 8 hours depending on the dosage used.

- Intermediate Insulin: (e.g. NPH insulin)- Usually taken in combination with a short acting insulin. Intermediate acting insulin starts to activate within the first hour of injecting and enters a period of peak activity lasting for 7 hours.

Sulfonylureas

- Sulfonylureas: This medication signals the pancreas to release insulin and help the body's cells use insulin better. This medicaiton can lower A1C levels ( AIC is defined as a measurement of the blood glucose after previous 2–3 months) by 1-2%.

Early diagnosis and interventive treatment can mean reduced incidence of complications such as cataracts and neuropathy. Since dogs are insulin dependent, oral drugs are not effective for them. They must be placed on insulin replacement therapy. Approved oral diabetes drugs can be helpful to sufferers of Type 2 diabetes because they work in one of three ways: by inducing the pancreas to produce more insulin, by allowing the body to more effectively use the insulin it produces, or by slowing the glucose absorption rate from the GI tract. Unapproved so-called "natural" remedies make similar claims for their products. All of this is based on the premise of having an endocrine pancreas with beta cells capable of producing insulin. Those with Type 1, or insulin-dependent diabetes, have beta cells which are permanently damaged, thus unable to produce insulin. This is the reason nothing other than insulin replacement therapy can be considered real and effective treatment. Canine diabetes means insulin dependency; insulin therapy must be continued for life.

The goal is to regulate the pet's blood glucose using insulin and some probable diet and daily routine changes. The process may take a few weeks or many months. It is basically the same as in Type 1 diabetic humans. The aim is to keep the blood glucose values in an acceptable range. The commonly recommended dosing method is by "starting low and going slow" as indicated for people with diabetes.

During the initial process of regulation and periodically thereafter, the effectiveness of the insulin dose at controlling blood glucose needs to be evaluated. This is done by a series of blood glucose tests called a curve. Blood samples are taken and tested at intervals of one to two hours over a 12- or 24-hour period. The results are generally transferred into graph form for easier interpretation. They are compared against the feeding and insulin injection times for judgment. The curve provides information regarding the action of the insulin in the animal. It is used to determine insulin dose adjustments, determine lowest and highest blood glucose levels, discover insulin duration and, in the case of continued hyperglycemia, whether the cause is insufficient insulin dose or Somogyi rebound, where blood glucose levels initially reach hypoglycemic levels and are brought to hyperglycemic ones by the body's counterregulatory hormones. Curves also provide evidence of insulin resistance which may be caused by medications other than insulin or by disorders other than diabetes which further testing can help identify.

Other diagnostic tests to determine the level of diabetic control are fructosamine and glycosylated hemoglobin (GHb) blood tests which can be useful especially if stress may be a factor. While anxiety or stress may influence the results of blood or urine glucose tests, both of these tests measure glycated proteins, which are not affected by them. Fructosamine testing provides information about blood glucose control for an approximate 2- to 4-week period, while GHb tests measure a 2- to 4-month period. Each of these tests has its own limitations and drawbacks and neither are intended to be replacements for blood glucose testing and curves, but are to be used to supplement the information gained from them. While HbA1c tests are a common diagnostic for diabetes in humans, there are no standards of measurement for use of the test in animals. This means the information from them may not be reliable.

The diabetic pet is considered regulated when its blood glucose levels remain within an acceptable range on a regular basis. Acceptable levels for dogs are between 5 and 10 mmol/L or 90 to 180 mg/dL. The range is wider for diabetic animals than non-diabetics, because insulin injections cannot replicate the accuracy of a working pancreas.

TCAs include imipramine, amitriptyline, desipramine, and nortriptyline. They are generally regarded as first or second-line treatment for DPN. Of the TCAs, imipramine has been the best studied. These medications are effective at decreasing painful symptoms but suffer from multiple side effects that are dose-dependent. One notable side effect is cardiac toxicity, which can lead to fatal abnormal heart rhythms. Additional common side effects include dry mouth, difficulty sleeping, and sedation. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.

Typical opioid medications, such as oxycodone, appear to be no more effective than placebo. In contrast, low-quality evidence supports a moderate benefit from the use of atypical opioids (e.g., tramadol and tapentadol), which also have SNRI properties. Opioid medications are recommended as second or third-line treatment for DPN.

Treatment depends upon the underlying cause:

- Hypoglycaemic diabetic coma: administration of the hormone glucagon to reverse the effects of insulin, or glucose given intravenously.

- Ketoacidotic diabetic coma: intravenous fluids, insulin and administration of potassium and sodium.

- Hyperosmolar diabetic coma: plenty of intravenous fluids, insulin, potassium and sodium given as soon as possible.

Many observational and clinical studies have been conducted to investigate the role of vitamins on diabetic complications,

In the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, vitamin supplementations were associated with 24% reduction on the risk of diabetes, observed during 20 years of follow-up.

Many observational studies and clinical trials have linked several vitamins with the pathological process of diabetes; these vitamins include folate, thiamine, β-carotene, and vitamin E, C, B12, and D.

- "Vitamin D:"

Vitamin D insufficiency is common in diabetics. Observational studies show that serum vitamin D is inversely associated with biomarkers of diabetes; impaired insulin secretion, insulin resistance, and glucose intolerance.

It has been suggested that vitamin D may induce beneficial effects on diabetic complications by modulating differentiation and growth of pancreatic β-cells and protecting these cells from apoptosis, thus improving β-cells functions and survival. Vitamin D has also been suggested to act on immune system and modulate inflammatory responses by influencing proliferation and differentiation of different immune cells., Moreover, deficiency of vitamin D may contribute to diabetic complications by inducing hyperparathyroidism, since elevated parathyroid hormone levels are associated with reduced β-cells function, impaired insulin sensitivity, and glucose intolerance. Finally, vitamin D may reduce the risk of vascular complications by modulating lipid profile.

- "Antioxidants" may have beneficial effects on diabetic complications by reducing blood pressure, attenuating oxidative stress and inflammatory biomarkers, improving lipid metabolism, insulin-mediated glucose disposal, and by enhancing endothelial function.

Vitamin C has been proposed to induce beneficial effects by two other mechanisms. It may replace glucose in many chemical reactions due to its similarity in structure, may prevent the non-enzymatic glycosylation of proteins, and might reduce glycated hemoglobin (HbA1c) levels. Secondly, vitamin C has also been suggested to play a role in lipid regulation as a controlling catabolism of cholesterol to bile acid.

Proper management of diabetes mellitus can prevent proximal diabetic neuropathy from ever occurring.

The incidence of proximal diabetic neuropathy incidence is thought to be correlated to blood glucose control in diabetics, and is likely reversible with better control.

Medication helps reduce the pain involved in proximal diabetic neuropathy. Most patients take oral medication that is prescribed by a doctor. Common types of medication used to treat diabetic amyotrophy include anticonvulsives (e.g. gabapentin, pregabalin) as well as opioid medications, although the latter category is not optimally indicated for neuropathic pain.

These medicines are designed to blunt the β-effect of adrenalin and related substances. Hence, if hypoglycemia occurs in someone who is using this type of drug, he/she may not experience the typical adrenergic warning symptoms such as tremor and palpitations. Again, the result is hypoglycemic unawareness. As noted above, beta blockers will also prevent adrenalin from stimulating the liver to make glucose, and therefore may make the hypoglycemia more severe and/or more protracted. Of all the hypoglycemia symptoms, sweating is typically not blocked by beta blockers.

Potassium replacement is often required as the metabolic problems are corrected. It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output.

Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12 liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1 L/h for the first few hours or until the condition stabilizes.

The blood glucose can usually be raised to normal within minutes with 15-20 grams of carbohydrate, although overtreatment should be avoided if at all possible. It can be taken as food or drink if the person is conscious and able to swallow. This amount of carbohydrate is contained in about 3-4 ounces (100-120 mL) of orange, apple, or grape juice, about 4-5 ounces (120-150 mL) of regular (non-diet) soda, about one slice of bread, about 4 crackers, or about 1 serving of most starchy foods. Starch is quickly digested to glucose, but adding fat or protein retards digestion. Composition of the treatment should be considered, as fruit juice is typically higher in fructose which takes the body longer to metabolize than simple dextrose alone. Following treatment, symptoms should begin to improve within 5 to 10 minutes, although full recovery may take 10–20 minutes. It should be noted that over treatment does not speed recovery, and will simply produce hyperglycemia afterwards, which ultimately will need to be corrected. On the other hand, since the excess of insulin over the amount required to normalize blood sugar may continue to reduce blood sugar levels after treatment has produced an initial normalization, continued monitoring is required to determine if further treatment is necessary.

Diabetes mellitus may be effectively managed by appropriate meal planning, increased physical activity and properly-instituted insulin treatment. Some tips for controlling diabetes in pregnancy include:

- Meals – Cut down sweets, eats three small meals and one to three snacks a day, maintain proper mealtimes, and include balanced fiber intake in the form of fruits, vegetables and whole-grains.

- Increased physical activity - walking, swimming/aquaerobics, etc.

- Monitor blood sugar level frequently, doctors may ask to check the blood glucose more often than usual.

- The blood sugar level should be below 95 mg/dl (5.3 mmol/l) on awakening, below 140 mg/dl (7.8 mmol/l) one hour after a meal and below 120 mg/dl (6.7 mmol/l) two hours after a meal.

- Each time when checking the blood sugar level, keep a proper record of the results and present to the health care team for evaluation and modification of the treatment. If blood sugar levels are above targets, a perinatal diabetes management team may suggest ways to achieve targets.

- Many may need extra insulin during pregnancy to reach their blood sugar target. Insulin is not harmful for the baby.

Treatment of diabetic foot can be challenging and prolonged; it may include orthopaedic appliances, antimicrobial drugs and topical dressings.

Most diabetic foot infections (DFIs) require treatment with systemic antibiotics. The choice of the initial antibiotic treatment depends on several factors such as the severity of the infection, whether the patient has received another antibiotic treatment for it, or whether the infection has been caused by a micro-organism that is known to be resistant to usual antibiotics (e.g. MRSA). The objective of antibiotic therapy is to stop the infection and ensure it does not spread.

It is unclear whether any particular antibiotic is better than any other for curing infection or avoiding amputation. One trial suggested that ertapenem with or without vancomycin is more effective than tigecycline for resolving DFIs. It is also generally unclear whether different antibiotics are associated with more or fewer adverse effects.

It is recommended however that the antibiotics used for treatment of diabetic foot ulcers should be used after deep tissue culture of the wound. Tissue culture and not pus swab culture should be done. Antibiotics should be used at correct doses in order to prevent the emergence of drug resistance.

Clinical Trials of NDM

- The research article is entitled, "A Successful Transition to sulfonamides treatment in male infant with novel neonatal diabetes mellitus (NDM) caused by the ABBC8 gene mutation and 3 years follow up". It is a case study on the transitioning of treatments from insulin therapy to sulfonamides therapy. NDM is not initiated by an autoimmune mechanism but mutations in K-sensitve channel, "KCNJ11, ABCC8" and "INS" genes are successful targets for changing treatments from insulin to sulfonamides therapy.

- Introduction: Within this study a two month old male was admitted into the intensive care unit, because the he was showing signs of diabetic ketoacidosis. Other symptoms include, respiratory tract infection, sporous, dehydration, reduced subcutaneous fat, Candida mucous infection. The infant's family history was negative for diseases of importance to hereditary and the eldest sibling was healthy.

- Experiment: The current treatment plan consist of therapy for ketoacidosis was started upon admissions into the hospital. Also, subcutaneous insulin was given (0.025-0.05 units/kg/h) and adjusted to the glycaemic profiles and the patient was converted to euglycaemic state. After 24 hours, oral intake of insulin started and treatment continued with subcutaneous short acting insulin then intermediate acting insulin plus 2 dosage of short acting insulin. A genetic analysis was conducted for NDM and mutation of KCNJ11, "ABCC8" and "INS" genes have been given. Sequence analysis showed a rare heterogeneous missense mutation, PF577L, in the patient's exon 12 of ABCC8 gene. This confirms diagnosis of NDM caused by heterozygous mutation in the SUR1 subunit of the pancreatic ATP-sensitive potassium channel, because his parents' white blood cells did not show signs of this mutation.

- Results: Switching from the insulin therapy to the sulfonamides was a successful treatment. It is the current regimen used to treat NDM.

- Discussion/Conclusion: ABCC8 gene produces SUR1 protein subunit that interacts with pancreatic ATP-sensitive potassium channel. When the channel opens a large amount of insulin is released. Mutations that occur in ABCC8 are associated with congential hyperinsulinism and PNDM or TNDM. Patients that have mutations in their potassium channel, improved their glucose levels with sulfonylurea regimen and glibenclamide showed successful results in managing glucose levels as well.

- A 2006 study showed that 90% of patients with a KCNJ11 mutation were able to successfully transition to sulfonylurea therapy.