If you have type 2 diabetes and an increased risk of heart disease, kidney problems, or heart failure, your treatment plan may look a little different. The goal is not only to control blood sugar, but also to protect your heart and kidneys and avoid side effects like low blood sugar.
Doctors usually choose medicines that lower blood sugar and protect the heart or kidneys:
In summary: If you have type 2 diabetes and a high risk of heart or kidney problems, your treatment will usually include medicines like SGLT-2 inhibitors or GLP-1 receptor agonists, sometimes together with metformin. The plan is always personalized to balance blood sugar control with heart and kidney protection, while avoiding low blood sugar.
The focus of diabetes therapy has shifted in recent years. Achieving the best possible blood glucose values is no longer the primary goal. In earlier guidelines, HbA1c, as the representative of good blood glucose control, was the target parameter upon which therapy was based. Today, treatment goals have been redefined. The two main therapeutic objectives are:
Since every patient is individually different, it is necessary before starting therapy to consider and define which treatment goals make sense for that particular patient. This is a joint task for both the patient and the physician. Any therapy imposed on the patient without taking into account their personal issues, wishes, and characteristics is bound to fail.
In the recommendations of the American Diabetes Association (ADA), the approach is described within a decision-making cycle. We deliberately use the American guidelines here. The revised version is published every January and reflects the most up-to-date state of scientific knowledge.
In the recommendations of the American Diabetes Association (ADA), the approach is described within a decision-making cycle.
Decision cycle for patient-centered glucose management in type 2 diabetes
Treatment goals:
Prevention of complications
Optimization of quality of life
Ensure regular appointments; initially, more frequent contact is desirable for DSMES
Set SMART goals
Specific, Measurable, Achievable, Realistic, Time-bound
Decision cycle for person-centered glycemic management in type 2 diabetes. Adapted from Davies et al. (246). BGM, blood glucose monitoring; BP, blood pressure; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CVD, atherosclerotic cardiovascular disease; DSMES, diabetes self-management education and support; HF, heart failure.
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The patient is at the center. The therapeutic goals are the prevention of complications and the improvement of quality of life.
To achieve this, the patient’s characteristics must first be assessed. Treatment goals and treatment plans must be developed together with the patient. Individual wishes and personal goals should be taken into account.
In type 2 diabetes therapy, not only blood glucose levels matter
Before starting therapy, it is important to be clear about what can realistically be achieved. Therapy is not just about trying to optimize blood glucose values. A patient with type 2 diabetes is usually overweight, has high blood pressure, lipid metabolism disorders, and impaired glucose metabolism. These conditions almost always occur together. It makes little sense to treat only one of these components. All must be addressed in order to reduce the risk of heart attack and stroke. For preventing stroke or heart attack, optimizing blood pressure and cholesterol levels is much more important than blood glucose values. However, blood glucose should not be neglected. Microvascular complications that can lead to blindness, kidney failure, and leg amputation can be effectively prevented or delayed through good glycemic control.
Avoiding weight gain and hypoglycemia
Good blood glucose control does not mean achieving the lowest possible values at any cost. Sulfonylureas, glitazones, and insulin lead to weight gain. In particular, insulin therapy can cause significant weight increase. Sulfonylureas and insulin can also cause hypoglycemia. These negative effects, however, do not mean that good blood glucose control should not be pursued. Good glycemic control should not be achieved at the expense of marked weight gain or at the cost of increased hypoglycemia risk.
Therefore, individual goals should be set for each patient. When choosing a treatment, the effects on weight, risk of hypoglycemia, and medication side effects should be considered. Overly complex regimens are not suitable for every patient.
The patient should be involved in the decisions regarding their treatment plan. This requires an informed and educated patient.
The treatment plan goals – the SMART goals – should be agreed upon with the patient. SMART means that the goals must be Specific, Measurable, Achievable, Realistic, and Time-limited.
To implement the action plan, physician visits are recommended at least every three months. At these visits, the patient’s well-being and the tolerability of the medication should be checked. Follow-up examinations include discussion of blood glucose control, clinical parameters including SMBG (self-monitored blood glucose), weight, physical activity (steps taken), long-term HbA1c, blood pressure, and blood lipids.
The individual decision-making cycle and action plan should be reviewed at least once a year.
Immediate initiation of therapy for type 2 diabetes
Treatment should begin as soon as type 2 diabetes mellitus is diagnosed. Initially, the treatment consists of agreeing on lifestyle modification goals with the patient and supporting them in achieving these goals. Key measures are the initiation of an exercise program and dietary changes aimed at weight reduction. These two aspects are described in detail in the chapters “Therapeutic pillars: nutrition and exercise” and “Weight loss helps in type 2 diabetes”.
Lifestyle modification is the foundation of successful diabetes therapy. In most cases, patients cannot carry out lifestyle changes on their own. They need support and education. With these measures, they should be guided toward self-management of their diabetes. For the healthcare provider, it is important to consider the social determinants that influence health.
In addition to lifestyle intervention, treatment options include oral medications (metformin, acarbose, sulfonylureas, thiazolidinediones), newer agents (DPP-4 inhibitors and incretin mimetics, SGLT-2 inhibitors), as well as insulin – in part also in combination. You can read more about these treatment options in the individual articles by following the respective links.
Pharmacological stepwise therapy in type 2 diabetes mellitus
In contrast to earlier guidelines, the recommendations of the American Diabetes Association (ADA) for pharmacological therapy in type 2 diabetes mellitus are no longer guided solely by blood glucose levels, but by the patient as a whole, considering comorbidities and risks for cardiovascular disease, heart failure, and chronic kidney disease.
The initial recommendations are a healthy lifestyle, diabetes self-management supported by structured education and continuous support, as well as taking into account the social determinants of health.
In earlier guidelines, the immediate initiation of metformin upon diagnosis was recommended. We continue to adhere to this recommendation: when no contraindications are observed, metformin is safe, and in our experience it already helps prevent progression from prediabetes to overt type 2 diabetes.A recent published study demonstrated the prevention of. progression from prediabetes to overt type 2 diabetes.
Knowler, William CAbbas, Caroline et al. Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial.The Lancet Diabetes & Endocrinology2025, Volume 13, Issue 6, 469 – 481
Moreover, it is very cost-effective. Increasingly, cancer has become a major risk factor for death in patients with type 2 diabetes. Metformin also reduces cancer risk. In contrast to the latest edition of the guidelines, we therefore continue to advocate for the immediate administration of metformin at the time of diagnosis. The new guidelines do not take into account the elevated risk of cancer-related death in patients with type 2 diabetes. Some studies suggest that this risk may even exceed the cardiovascular risk.
The 2025 guidelines focus on the goal of reducing cardiovascular and renal risk factors in high-risk patients with type 2 diabetes mellitus.
Which pharmacological treatment is initiated depends on whether the patient is at high risk for, or already has established, atherosclerotic cardiovascular disease (ASCVD), whether chronic kidney disease (CKD) is present, or whether the patient has heart failure (HF).
If, in the above risk constellations, further cardiovascular or chronic kidney disease risk reduction is required, management of metabolic comorbidities is necessary. If additional glucose lowering is needed and there is also mild risk of metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH), then agents with proven efficacy in MASLD or MASH should be added (GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonists, or pioglitazone in combination with a GLP-1 receptor agonist).
In the case of decompensated cirrhosis, insulin therapy should be used.
ACEi, angiotensin-converting enzyme inhibitor; ACR, albumin-to-creatinine ratio; ARB, angiotensin receptor blocker; ASCVD, atherosclerotic cardiovascular disease; CGM, continuous glucose monitoring; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidyl peptidase 4 inhibitor; DSMES, diabetes self-management education and support; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; MACE, major adverse cardiovascular events; MASH, metabolic dysfunction–associated steatohepatitis; MASLD, metabolic dysfunction–associated steatotic liver disease; MI, myocardial infarction; SDOH, social determinants of health; SGLT2i, sodium–glucose cotransporter 2 inhibitor; T2D, type 2 diabetes.
If you have type 2 diabetes but no heart disease, kidney disease, or heart failure, the main goals of treatment are:
In summary:
If there is no increased risk for cardiovascular or arteriosclerotic disease, chronic renal insufficiency, or heart failure, treatment should begin by defining goals for blood glucose control and weight management. For pharmacologic therapy, metformin is suitable, and if this is not sufficient, it can be combined, for example, with DPP-4 inhibitors. We advise against combining metformin with sulfonylureas due to the risk of hypoglycemia and weight gain. Hypoglycemia should especially be avoided in high-risk patients and in older patients.
Although sulfonylureas are inexpensive and some do not increase cardiovascular risk, all studies have shown that sulfonylureas shorten the functional capacity of beta cells to produce insulin. Treatment with sulfonylureas provides only one to two years of improved glycemic control and subsequently places the patient in a worse position due to loss of beta-cell capacity. We therefore do not recommend sulfonylureas.
Type 2 diabetes mellitus is a progressive disease. With monotherapy, it is often only possible for a limited number of years to achieve the individually defined HbA1c targets. It has been shown that with an initial combination therapy of metformin and vildagliptin (a DPP-4 inhibitor), deterioration of glycemic control occurs significantly more slowly compared to sequential therapy, where metformin is used first and escalation to further therapy occurs only after monotherapy fails. This likely applies not only to vildagliptin but also to combination therapies with GLP-1 receptor agonists and SGLT-2 inhibitors. If HbA1c is 1.5–2% above the desired target, initial combination therapy should be considered.
For patients without chronic kidney disease, cardiovascular disease, or increased risk of these conditions, the primary goal is blood glucose control and weight management.
If HbA1c remains above target despite overweight or insufficient glucose lowering, other barriers contributing to hyperglycemia should be identified. Important measures then include diabetes self-management education, self-monitoring of blood glucose or CGM, and identifying social determinants of health.
Target values in patients with long diabetes duration
In patients with type 2 diabetes mellitus, the risk of cardiovascular death is increased. If blood glucose is lowered too aggressively in patients with a diabetes duration of more than 15 years, the risk of cardiovascular death rises (ACCORD, VADT studies). Therefore, it does not make sense to pursue strict treatment goals by all possible means in patients with long-standing diabetes. The reason why the risk of death is increased is not fully understood. One possible explanation is that hypoglycemia, which occurs more frequently with overly strict glycemic control, may trigger the release of stress hormones such as catecholamines, which can lead to cardiovascular death.
In patients with long diabetes duration and known cardiovascular disease, a cautious reduction and improvement of blood glucose levels is therefore required. Whenever possible, medications that do not cause hypoglycemia should be used. Since insulin therapy is often necessary in long-standing diabetes, individual adjustment of treatment targets is essential to avoid hypoglycemia.
For patients without chronic kidney disease, cardiovascular disease, or an increased risk of these conditions, the main treatment goal is blood glucose control and weight management.